Where do the protons in the mitochondrial intermembrane space originally come from?

Where do the protons in the mitochondrial intermembrane space originally come from?

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I'm currently reviewing this concept in cellular respiration. The book which I'm using is Reece, Minorsky, Campbell's Biology and while it does a good job at explaining the process involved in the electron chain transport. I think it lacks of clearing out my doubts concerning initial protons.

Let me explain, the part where I'm stuck at is, where do originally the protons in the mitochondrial intermembrane space come from?. I understand that there is a proton gradient and the translocation of this protons in the proton pump is key during the electron shuttle process but, how did those initial protons come?. In other words, during the formation of the mitochondria in the cell, have they always been there? or are they part of some bigger molecule and that those protons are detached from them so that there is an initial gradient that triggers the process for the first time?. In other words, how does that initial spark or kick off begins?.

In most animations I've found, the explanations take for granted that the protons are freely moving in the intermembrane space such as here and also here but what do those videos lack is the explanation of how (as mentioned above) do those protons got there in the first place.

I'd like somebody could help me to clear out this doubt. I feel that as an addition to the answer, I'd like to know how does the mitochondria forms in the cell?. Since I believe there might be steps involved, I'd appreciate that the answer could explain those steps so I could easily understand, because as mentioned. I'm still confused on that part as well.


Chemiosmosis is the movement of ions across a semipermeable membrane bound structure, down their electrochemical gradient. An example of this would be the formation of adenosine triphosphate (ATP) by the movement of hydrogen ions (H + ) across a membrane during cellular respiration or photosynthesis.

Hydrogen ions, or protons, will diffuse from an area of high proton concentration to an area of lower proton concentration, and an electrochemical concentration gradient of protons across a membrane can be harnessed to make ATP. This process is related to osmosis, the diffusion of water across a membrane, which is why it is called "chemiosmosis".

ATP synthase is the enzyme that makes ATP by chemiosmosis. It allows protons to pass through the membrane and uses the free energy difference to phosphorylate adenosine diphosphate (ADP), making ATP. The generation of ATP by chemiosmosis occurs in mitochondria and chloroplasts, as well as in most bacteria and archaea, an electron transport chain pumps H + ions (protons) in the thylakoid spaces through thylakoid membranes to stroma (fluid). The energy from the electron movement through electron transport chains cross through ATP synthase which allows the proton to pass through them and use this free energy difference to photophosphorylate ADP making ATP.


Mitochondria may have a number of different shapes. [23] A mitochondrion contains outer and inner membranes composed of phospholipid bilayers and proteins. [17] The two membranes have different properties. Because of this double-membraned organization, there are five distinct parts to a mitochondrion:

  1. The outer mitochondrial membrane,
  2. The intermembrane space (the space between the outer and inner membranes),
  3. The inner mitochondrial membrane,
  4. The cristae space (formed by infoldings of the inner membrane), and
  5. The matrix (space within the inner membrane).

Mitochondria stripped of their outer membrane are called mitoplasts.

Outer membrane Edit

The outer mitochondrial membrane, which encloses the entire organelle, is 60 to 75 angstroms (Å) thick. It has a protein-to-phospholipid ratio similar to that of the cell membrane (about 1:1 by weight). It contains large numbers of integral membrane proteins called porins. A major trafficking protein is the pore-forming voltage-dependent anion channel (VDAC). The VDAC is the primary transporter of nucleotides, ions and metabolites between the cytosol and the intermembrane space. [24] [25] It is formed as a beta barrel that spans the outer membrane, similar to that in the gram-negative bacterial membrane. [26] Larger proteins can enter the mitochondrion if a signaling sequence at their N-terminus binds to a large multisubunit protein called translocase in the outer membrane, which then actively moves them across the membrane. [27] Mitochondrial pro-proteins are imported through specialised translocation complexes.

The outer membrane also contains enzymes involved in such diverse activities as the elongation of fatty acids, oxidation of epinephrine, and the degradation of tryptophan. These enzymes include monoamine oxidase, rotenone-insensitive NADH-cytochrome c-reductase, kynurenine hydroxylase and fatty acid Co-A ligase. Disruption of the outer membrane permits proteins in the intermembrane space to leak into the cytosol, leading to cell death. [28] The mitochondrial outer membrane can associate with the endoplasmic reticulum (ER) membrane, in a structure called MAM (mitochondria-associated ER-membrane). This is important in the ER-mitochondria calcium signaling and is involved in the transfer of lipids between the ER and mitochondria. [29] Outside the outer membrane there are small (diameter: 60Å) particles named sub-units of Parson.

Intermembrane space Edit

The mitochondrial intermembrane space is the space between the outer membrane and the inner membrane. It is also known as perimitochondrial space. Because the outer membrane is freely permeable to small molecules, the concentrations of small molecules, such as ions and sugars, in the intermembrane space is the same as in the cytosol. [17] However, large proteins must have a specific signaling sequence to be transported across the outer membrane, so the protein composition of this space is different from the protein composition of the cytosol. One protein that is localized to the intermembrane space in this way is cytochrome c. [28]

Inner membrane Edit

The inner mitochondrial membrane contains proteins with three types of functions: [17]

  1. Those that perform the electron transport chainredox reactions , which generates ATP in the matrix
  2. Specific transport proteins that regulate metabolite passage into and out of the mitochondrial matrix

It contains more than 151 different polypeptides, and has a very high protein-to-phospholipid ratio (more than 3:1 by weight, which is about 1 protein for 15 phospholipids). The inner membrane is home to around 1/5 of the total protein in a mitochondrion. [30] Additionally, the inner membrane is rich in an unusual phospholipid, cardiolipin. This phospholipid was originally discovered in cow hearts in 1942, and is usually characteristic of mitochondrial and bacterial plasma membranes. [31] Cardiolipin contains four fatty acids rather than two, and may help to make the inner membrane impermeable. [17] Unlike the outer membrane, the inner membrane does not contain porins, and is highly impermeable to all molecules. Almost all ions and molecules require special membrane transporters to enter or exit the matrix. Proteins are ferried into the matrix via the translocase of the inner membrane (TIM) complex or via OXA1L. [27] In addition, there is a membrane potential across the inner membrane, formed by the action of the enzymes of the electron transport chain. Inner membrane fusion is mediated by the inner membrane protein OPA1. [32]

Cristae Edit

The inner mitochondrial membrane is compartmentalized into numerous folds called cristae, which expand the surface area of the inner mitochondrial membrane, enhancing its ability to produce ATP. For typical liver mitochondria, the area of the inner membrane is about five times as large as the outer membrane. This ratio is variable and mitochondria from cells that have a greater demand for ATP, such as muscle cells, contain even more cristae. Mitochondria within the same cell can have substantially different crista-density, with the ones that are required to produce more energy having much more crista-membrane surface. [33] These folds are studded with small round bodies known as F1 particles or oxysomes. [34]

Matrix Edit

The matrix is the space enclosed by the inner membrane. It contains about 2/3 of the total proteins in a mitochondrion. [17] The matrix is important in the production of ATP with the aid of the ATP synthase contained in the inner membrane. The matrix contains a highly concentrated mixture of hundreds of enzymes, special mitochondrial ribosomes, tRNA, and several copies of the mitochondrial DNA genome. Of the enzymes, the major functions include oxidation of pyruvate and fatty acids, and the citric acid cycle. [17] The DNA molecules are packaged into nucleoids by proteins, one of which is TFAM. [35]

The most prominent roles of mitochondria are to produce the energy currency of the cell, ATP (i.e., phosphorylation of ADP), through respiration and to regulate cellular metabolism. [18] The central set of reactions involved in ATP production are collectively known as the citric acid cycle, or the Krebs cycle. However, the mitochondrion has many other functions in addition to the production of ATP.

Energy conversion Edit

A dominant role for the mitochondria is the production of ATP, as reflected by the large number of proteins in the inner membrane for this task. This is done by oxidizing the major products of glucose: pyruvate, and NADH, which are produced in the cytosol. [18] This type of cellular respiration, known as aerobic respiration, is dependent on the presence of oxygen, which provides most of the energy released. [36] When oxygen is limited, the glycolytic products will be metabolized by anaerobic fermentation, a process that is independent of the mitochondria. [18] The production of ATP from glucose and oxygen has an approximately 13-times higher yield during aerobic respiration compared to fermentation. [37] Plant mitochondria can also produce a limited amount of ATP either by breaking the sugar produced during photosynthesis or without oxygen by using the alternate substrate nitrite. [38] ATP crosses out through the inner membrane with the help of a specific protein, and across the outer membrane via porins. [39] ADP returns via the same route.

Pyruvate and the citric acid cycle Edit

Pyruvate molecules produced by glycolysis are actively transported across the inner mitochondrial membrane, and into the matrix where they can either be oxidized and combined with coenzyme A to form CO2, acetyl-CoA, and NADH, [18] or they can be carboxylated (by pyruvate carboxylase) to form oxaloacetate. This latter reaction "fills up" the amount of oxaloacetate in the citric acid cycle and is therefore an anaplerotic reaction, increasing the cycle's capacity to metabolize acetyl-CoA when the tissue's energy needs (e.g., in muscle) are suddenly increased by activity. [40]

In the citric acid cycle, all the intermediates (e.g. citrate, iso-citrate, alpha-ketoglutarate, succinate, fumarate, malate and oxaloacetate) are regenerated during each turn of the cycle. Adding more of any of these intermediates to the mitochondrion therefore means that the additional amount is retained within the cycle, increasing all the other intermediates as one is converted into the other. Hence, the addition of any one of them to the cycle has an anaplerotic effect, and its removal has a cataplerotic effect. These anaplerotic and cataplerotic reactions will, during the course of the cycle, increase or decrease the amount of oxaloacetate available to combine with acetyl-CoA to form citric acid. This in turn increases or decreases the rate of ATP production by the mitochondrion, and thus the availability of ATP to the cell. [40]

Acetyl-CoA, on the other hand, derived from pyruvate oxidation, or from the beta-oxidation of fatty acids, is the only fuel to enter the citric acid cycle. With each turn of the cycle one molecule of acetyl-CoA is consumed for every molecule of oxaloacetate present in the mitochondrial matrix, and is never regenerated. It is the oxidation of the acetate portion of acetyl-CoA that produces CO2 and water, with the energy thus released captured in the form of ATP. [40]

In the liver, the carboxylation of cytosolic pyruvate into intra-mitochondrial oxaloacetate is an early step in the gluconeogenic pathway, which converts lactate and de-aminated alanine into glucose, [18] [40] under the influence of high levels of glucagon and/or epinephrine in the blood. [40] Here, the addition of oxaloacetate to the mitochondrion does not have a net anaplerotic effect, as another citric acid cycle intermediate (malate) is immediately removed from the mitochondrion to be converted into cytosolic oxaloacetate, which is ultimately converted into glucose, in a process that is almost the reverse of glycolysis. [40]

The enzymes of the citric acid cycle are located in the mitochondrial matrix, with the exception of succinate dehydrogenase, which is bound to the inner mitochondrial membrane as part of Complex II. [41] The citric acid cycle oxidizes the acetyl-CoA to carbon dioxide, and, in the process, produces reduced cofactors (three molecules of NADH and one molecule of FADH2) that are a source of electrons for the electron transport chain, and a molecule of GTP (that is readily converted to an ATP). [18]

NADH and FADH2: the electron transport chain Edit

The electrons from NADH and FADH2 are transferred to oxygen (O2), an energy-rich molecule, [36] and hydrogen (protons) in several steps via the electron transport chain. NADH and FADH2 molecules are produced within the matrix via the citric acid cycle but are also produced in the cytoplasm by glycolysis. Reducing equivalents from the cytoplasm can be imported via the malate-aspartate shuttle system of antiporter proteins or feed into the electron transport chain using a glycerol phosphate shuttle. [18] Protein complexes in the inner membrane (NADH dehydrogenase (ubiquinone), cytochrome c reductase, and cytochrome c oxidase) perform the transfer, and the incremental release of energy is used to pump protons (H + ) into the intermembrane space. This process is efficient, but a small percentage of electrons may prematurely reduce oxygen, forming reactive oxygen species such as superoxide. [18] This can cause oxidative stress in the mitochondria and may contribute to the decline in mitochondrial function associated with the aging process. [42]

As the proton concentration increases in the intermembrane space, a strong electrochemical gradient is established across the inner membrane. The protons can return to the matrix through the ATP synthase complex, and their potential energy is used to synthesize ATP from ADP and inorganic phosphate (Pi). [18] This process is called chemiosmosis, and was first described by Peter Mitchell, [43] [44] who was awarded the 1978 Nobel Prize in Chemistry for his work. Later, part of the 1997 Nobel Prize in Chemistry was awarded to Paul D. Boyer and John E. Walker for their clarification of the working mechanism of ATP synthase. [45]

Heat production Edit

Under certain conditions, protons can re-enter the mitochondrial matrix without contributing to ATP synthesis. This process is known as proton leak or mitochondrial uncoupling and is due to the facilitated diffusion of protons into the matrix. The process results in the unharnessed potential energy of the proton electrochemical gradient being released as heat. [18] The process is mediated by a proton channel called thermogenin, or UCP1. [46] Thermogenin is primarily found in brown adipose tissue, or brown fat, and is responsible for non-shivering thermogenesis. Brown adipose tissue is found in mammals, and is at its highest levels in early life and in hibernating animals. In humans, brown adipose tissue is present at birth and decreases with age. [46]

Storage of calcium ions Edit

The concentrations of free calcium in the cell can regulate an array of reactions and is important for signal transduction in the cell. Mitochondria can transiently store calcium, a contributing process for the cell's homeostasis of calcium. [47] [48] Their ability to rapidly take in calcium for later release makes them good "cytosolic buffers" for calcium. [49] [50] [51] The endoplasmic reticulum (ER) is the most significant storage site of calcium, [52] and there is a significant interplay between the mitochondrion and ER with regard to calcium. [53] The calcium is taken up into the matrix by the mitochondrial calcium uniporter on the inner mitochondrial membrane. [54] It is primarily driven by the mitochondrial membrane potential. [48] Release of this calcium back into the cell's interior can occur via a sodium-calcium exchange protein or via "calcium-induced-calcium-release" pathways. [54] This can initiate calcium spikes or calcium waves with large changes in the membrane potential. These can activate a series of second messenger system proteins that can coordinate processes such as neurotransmitter release in nerve cells and release of hormones in endocrine cells. [55]

Ca 2+ influx to the mitochondrial matrix has recently been implicated as a mechanism to regulate respiratory bioenergetics by allowing the electrochemical potential across the membrane to transiently "pulse" from ΔΨ-dominated to pH-dominated, facilitating a reduction of oxidative stress. [56] In neurons, concomitant increases in cytosolic and mitochondrial calcium act to synchronize neuronal activity with mitochondrial energy metabolism. Mitochondrial matrix calcium levels can reach the tens of micromolar levels, which is necessary for the activation of isocitrate dehydrogenase, one of the key regulatory enzymes of the Krebs cycle. [57]

Cellular proliferation regulation Edit

The relationship between cellular proliferation and mitochondria has been investigated. Tumor cells require ample ATP to synthesize bioactive compounds such as lipids, proteins, and nucleotides for rapid proliferation. [58] The majority of ATP in tumor cells is generated via the oxidative phosphorylation pathway (OxPhos). [59] Interference with OxPhos cause cell cycle arrest suggesting that mitochondria play a role in cell proliferation. [59] Mitochondrial ATP production is also vital for cell division and differentiation in infection [60] in addition to basic functions in the cell including the regulation of cell volume, solute concentration, and cellular architecture. [61] [62] [63] ATP levels differ at various stages of the cell cycle suggesting that there is a relationship between the abundance of ATP and the cell's ability to enter a new cell cycle. [64] ATP's role in the basic functions of the cell make the cell cycle sensitive to changes in the availability of mitochondrial derived ATP. [64] The variation in ATP levels at different stages of the cell cycle support the hypothesis that mitochondria play an important role in cell cycle regulation. [64] Although the specific mechanisms between mitochondria and the cell cycle regulation is not well understood, studies have shown that low energy cell cycle checkpoints monitor the energy capability before committing to another round of cell division. [9]

Additional functions Edit

Mitochondria play a central role in many other metabolic tasks, such as:

  • Signaling through mitochondrial reactive oxygen species[65]
  • Regulation of the membrane potential[18] -programmed cell death [66]
  • Calcium signaling (including calcium-evoked apoptosis) [67]
  • Regulation of cellular metabolism[9]
  • Certain heme synthesis reactions [68](see also: porphyrin) synthesis. [49]
  • Hormonal signaling [69] Mitochondria are sensitive and responsive to hormones, in part by the action of mitochondrial estrogen receptors (mtERs). These receptors have been found in various tissues and cell types, including brain [70] and heart [71]
  • Immune signaling [72]
  • Neuronal mitochondria also contribute to cellular quality control by reporting neuronal status towards microglia through specialised somatic-junctions. [73]

Some mitochondrial functions are performed only in specific types of cells. For example, mitochondria in liver cells contain enzymes that allow them to detoxify ammonia, a waste product of protein metabolism. A mutation in the genes regulating any of these functions can result in mitochondrial diseases.

Mitochondria (and related structures) are found in all eukaryotes (except two—the Oxymonad Monocercomonoides and Henneguya salminicola). [5] [6] [7] [74] Although commonly depicted as bean-like structures they form a highly dynamic network in the majority of cells where they constantly undergo fission and fusion. The population of all the mitochondria of a given cell constitutes the chondriome. [75] Mitochondria vary in number and location according to cell type. A single mitochondrion is often found in unicellular organisms, while human liver cells have about 1000–2000 mitochondria per cell, making up 1/5 of the cell volume. [17] The mitochondrial content of otherwise similar cells can vary substantially in size and membrane potential, [76] with differences arising from sources including uneven partitioning at cell divisions, leading to extrinsic differences in ATP levels and downstream cellular processes. [77] The mitochondria can be found nestled between myofibrils of muscle or wrapped around the sperm flagellum. [17] Often, they form a complex 3D branching network inside the cell with the cytoskeleton. The association with the cytoskeleton determines mitochondrial shape, which can affect the function as well: [78] different structures of the mitochondrial network may afford the population a variety of physical, chemical, and signalling advantages or disadvantages. [79] Mitochondria in cells are always distributed along microtubules and the distribution of these organelles is also correlated with the endoplasmic reticulum. [80] Recent evidence suggests that vimentin, one of the components of the cytoskeleton, is also critical to the association with the cytoskeleton. [81]

Mitochondria-associated ER membrane (MAM) Edit

The mitochondria-associated ER membrane (MAM) is another structural element that is increasingly recognized for its critical role in cellular physiology and homeostasis. Once considered a technical snag in cell fractionation techniques, the alleged ER vesicle contaminants that invariably appeared in the mitochondrial fraction have been re-identified as membranous structures derived from the MAM—the interface between mitochondria and the ER. [82] Physical coupling between these two organelles had previously been observed in electron micrographs and has more recently been probed with fluorescence microscopy. [82] Such studies estimate that at the MAM, which may comprise up to 20% of the mitochondrial outer membrane, the ER and mitochondria are separated by a mere 10–25 nm and held together by protein tethering complexes. [82] [29] [83]

Purified MAM from subcellular fractionation is enriched in enzymes involved in phospholipid exchange, in addition to channels associated with Ca 2+ signaling. [82] [83] These hints of a prominent role for the MAM in the regulation of cellular lipid stores and signal transduction have been borne out, with significant implications for mitochondrial-associated cellular phenomena, as discussed below. Not only has the MAM provided insight into the mechanistic basis underlying such physiological processes as intrinsic apoptosis and the propagation of calcium signaling, but it also favors a more refined view of the mitochondria. Though often seen as static, isolated 'powerhouses' hijacked for cellular metabolism through an ancient endosymbiotic event, the evolution of the MAM underscores the extent to which mitochondria have been integrated into overall cellular physiology, with intimate physical and functional coupling to the endomembrane system.

Phospholipid transfer Edit

The MAM is enriched in enzymes involved in lipid biosynthesis, such as phosphatidylserine synthase on the ER face and phosphatidylserine decarboxylase on the mitochondrial face. [84] [85] Because mitochondria are dynamic organelles constantly undergoing fission and fusion events, they require a constant and well-regulated supply of phospholipids for membrane integrity. [86] [87] But mitochondria are not only a destination for the phospholipids they finish synthesis of rather, this organelle also plays a role in inter-organelle trafficking of the intermediates and products of phospholipid biosynthetic pathways, ceramide and cholesterol metabolism, and glycosphingolipid anabolism. [85] [87]

Such trafficking capacity depends on the MAM, which has been shown to facilitate transfer of lipid intermediates between organelles. [84] In contrast to the standard vesicular mechanism of lipid transfer, evidence indicates that the physical proximity of the ER and mitochondrial membranes at the MAM allows for lipid flipping between opposed bilayers. [87] Despite this unusual and seemingly energetically unfavorable mechanism, such transport does not require ATP. [87] Instead, in yeast, it has been shown to be dependent on a multiprotein tethering structure termed the ER-mitochondria encounter structure, or ERMES, although it remains unclear whether this structure directly mediates lipid transfer or is required to keep the membranes in sufficiently close proximity to lower the energy barrier for lipid flipping. [87] [88]

The MAM may also be part of the secretory pathway, in addition to its role in intracellular lipid trafficking. In particular, the MAM appears to be an intermediate destination between the rough ER and the Golgi in the pathway that leads to very-low-density lipoprotein, or VLDL, assembly and secretion. [85] [89] The MAM thus serves as a critical metabolic and trafficking hub in lipid metabolism.

Calcium signaling Edit

A critical role for the ER in calcium signaling was acknowledged before such a role for the mitochondria was widely accepted, in part because the low affinity of Ca 2+ channels localized to the outer mitochondrial membrane seemed to contradict this organelle's purported responsiveness to changes in intracellular Ca 2+ flux. [82] [52] But the presence of the MAM resolves this apparent contradiction: the close physical association between the two organelles results in Ca 2+ microdomains at contact points that facilitate efficient Ca 2+ transmission from the ER to the mitochondria. [82] Transmission occurs in response to so-called "Ca 2+ puffs" generated by spontaneous clustering and activation of IP3R, a canonical ER membrane Ca 2+ channel. [82] [29]

The fate of these puffs—in particular, whether they remain restricted to isolated locales or integrated into Ca 2+ waves for propagation throughout the cell—is determined in large part by MAM dynamics. Although reuptake of Ca 2+ by the ER (concomitant with its release) modulates the intensity of the puffs, thus insulating mitochondria to a certain degree from high Ca 2+ exposure, the MAM often serves as a firewall that essentially buffers Ca 2+ puffs by acting as a sink into which free ions released into the cytosol can be funneled. [82] [90] [91] This Ca 2+ tunneling occurs through the low-affinity Ca 2+ receptor VDAC1, which recently has been shown to be physically tethered to the IP3R clusters on the ER membrane and enriched at the MAM. [82] [29] [92] The ability of mitochondria to serve as a Ca 2+ sink is a result of the electrochemical gradient generated during oxidative phosphorylation, which makes tunneling of the cation an exergonic process. [92] Normal, mild calcium influx from cytosol into the mitochondrial matrix causes transient depolarization that is corrected by pumping out protons.

But transmission of Ca 2+ is not unidirectional rather, it is a two-way street. [52] The properties of the Ca 2+ pump SERCA and the channel IP3R present on the ER membrane facilitate feedback regulation coordinated by MAM function. In particular, the clearance of Ca 2+ by the MAM allows for spatio-temporal patterning of Ca 2+ signaling because Ca 2+ alters IP3R activity in a biphasic manner. [82] SERCA is likewise affected by mitochondrial feedback: uptake of Ca 2+ by the MAM stimulates ATP production, thus providing energy that enables SERCA to reload the ER with Ca 2+ for continued Ca 2+ efflux at the MAM. [90] [92] Thus, the MAM is not a passive buffer for Ca 2+ puffs rather it helps modulate further Ca 2+ signaling through feedback loops that affect ER dynamics.

Regulating ER release of Ca 2+ at the MAM is especially critical because only a certain window of Ca 2+ uptake sustains the mitochondria, and consequently the cell, at homeostasis. Sufficient intraorganelle Ca 2+ signaling is required to stimulate metabolism by activating dehydrogenase enzymes critical to flux through the citric acid cycle. [93] [94] However, once Ca 2+ signaling in the mitochondria passes a certain threshold, it stimulates the intrinsic pathway of apoptosis in part by collapsing the mitochondrial membrane potential required for metabolism. [82] Studies examining the role of pro- and anti-apoptotic factors support this model for example, the anti-apoptotic factor Bcl-2 has been shown to interact with IP3Rs to reduce Ca 2+ filling of the ER, leading to reduced efflux at the MAM and preventing collapse of the mitochondrial membrane potential post-apoptotic stimuli. [82] Given the need for such fine regulation of Ca 2+ signaling, it is perhaps unsurprising that dysregulated mitochondrial Ca 2+ has been implicated in several neurodegenerative diseases, while the catalogue of tumor suppressors includes a few that are enriched at the MAM. [92]

Molecular basis for tethering Edit

Recent advances in the identification of the tethers between the mitochondrial and ER membranes suggest that the scaffolding function of the molecular elements involved is secondary to other, non-structural functions. In yeast, ERMES, a multiprotein complex of interacting ER- and mitochondrial-resident membrane proteins, is required for lipid transfer at the MAM and exemplifies this principle. One of its components, for example, is also a constituent of the protein complex required for insertion of transmembrane beta-barrel proteins into the lipid bilayer. [87] However, a homologue of the ERMES complex has not yet been identified in mammalian cells. Other proteins implicated in scaffolding likewise have functions independent of structural tethering at the MAM for example, ER-resident and mitochondrial-resident mitofusins form heterocomplexes that regulate the number of inter-organelle contact sites, although mitofusins were first identified for their role in fission and fusion events between individual mitochondria. [82] Glucose-related protein 75 (grp75) is another dual-function protein. In addition to the matrix pool of grp75, a portion serves as a chaperone that physically links the mitochondrial and ER Ca 2+ channels VDAC and IP3R for efficient Ca 2+ transmission at the MAM. [82] [29] Another potential tether is Sigma-1R, a non-opioid receptor whose stabilization of ER-resident IP3R may preserve communication at the MAM during the metabolic stress response. [95] [96]

Perspective Edit

The MAM is a critical signaling, metabolic, and trafficking hub in the cell that allows for the integration of ER and mitochondrial physiology. Coupling between these organelles is not simply structural but functional as well and critical for overall cellular physiology and homeostasis. The MAM thus offers a perspective on mitochondria that diverges from the traditional view of this organelle as a static, isolated unit appropriated for its metabolic capacity by the cell. [97] Instead, this mitochondrial-ER interface emphasizes the integration of the mitochondria, the product of an endosymbiotic event, into diverse cellular processes. Recently it has also been shown, that mitochondria and MAM-s in neurons are anchored to specialised intercellular communication sites (so called somatic-junctions). Microglial processes monitor and protect neuronal functions at these sites, and MAM-s are supposed to have an important role in this type of cellular quality-control. [73]

There are two hypotheses about the origin of mitochondria: endosymbiotic and autogenous. The endosymbiotic hypothesis suggests that mitochondria were originally prokaryotic cells, capable of implementing oxidative mechanisms that were not possible for eukaryotic cells they became endosymbionts living inside the eukaryote. [98] In the autogenous hypothesis, mitochondria were born by splitting off a portion of DNA from the nucleus of the eukaryotic cell at the time of divergence with the prokaryotes this DNA portion would have been enclosed by membranes, which could not be crossed by proteins. Since mitochondria have many features in common with bacteria, the endosymbiotic hypothesis is more widely accepted. [98] [99]

A mitochondrion contains DNA, which is organized as several copies of a single, usually circular chromosome. This mitochondrial chromosome contains genes for redox proteins, such as those of the respiratory chain. The CoRR hypothesis proposes that this co-location is required for redox regulation. The mitochondrial genome codes for some RNAs of ribosomes, and the 22 tRNAs necessary for the translation of mRNAs into protein. The circular structure is also found in prokaryotes. The proto-mitochondrion was probably closely related to Rickettsia. [100] [101] However, the exact relationship of the ancestor of mitochondria to the alphaproteobacteria and whether the mitochondrion was formed at the same time or after the nucleus, remains controversial. [102] For example, it has been suggested that the SAR11 clade of bacteria shares a relatively recent common ancestor with the mitochondria, [103] while phylogenomic analyses indicate that mitochondria evolved from a proteobacteria lineage that is closely related to or a member of alphaproteobacteria. [104] [105]

Subgroups Ib, II, IIIa, IIIb, IV and V

The ribosomes coded for by the mitochondrial DNA are similar to those from bacteria in size and structure. [107] They closely resemble the bacterial 70S ribosome and not the 80S cytoplasmic ribosomes, which are coded for by nuclear DNA.

The endosymbiotic relationship of mitochondria with their host cells was popularized by Lynn Margulis. [108] The endosymbiotic hypothesis suggests that mitochondria descended from bacteria that somehow survived endocytosis by another cell, and became incorporated into the cytoplasm. The ability of these bacteria to conduct respiration in host cells that had relied on glycolysis and fermentation would have provided a considerable evolutionary advantage. This symbiotic relationship probably developed 1.7 to 2 billion years ago. [109] [110] A few groups of unicellular eukaryotes have only vestigial mitochondria or derived structures: the microsporidians, metamonads, and archamoebae. [111] These groups appear as the most primitive eukaryotes on phylogenetic trees constructed using rRNA information, which once suggested that they appeared before the origin of mitochondria. However, this is now known to be an artifact of long-branch attraction—they are derived groups and retain genes or organelles derived from mitochondria (e. g., mitosomes and hydrogenosomes). [4] Hydrogenosomes, mitosomes, and related organelles as found in some loricifera (e. g. Spinoloricus) [112] [113] and myxozoa (e. g. Henneguya zschokkei) are together classified as MROs, mitochondrion-related organelles. [114] [115]

Monocercomonoides appear to have lost their mitochondria completely and at least some of the mitochondrial functions seem to be carried out by cytoplasmic proteins now. [116]

Mitochondria contain their own genome. The human mitochondrial genome is a circular DNA molecule of about 16 kilobases. [117] It encodes 37 genes: 13 for subunits of respiratory complexes I, III, IV and V, 22 for mitochondrial tRNA (for the 20 standard amino acids, plus an extra gene for leucine and serine), and 2 for rRNA. [117] One mitochondrion can contain two to ten copies of its DNA. [118]

As in prokaryotes, there is a very high proportion of coding DNA and an absence of repeats. Mitochondrial genes are transcribed as multigenic transcripts, which are cleaved and polyadenylated to yield mature mRNAs. Most proteins necessary for mitochondrial function are encoded by genes in the cell nucleus and the corresponding proteins are imported into the mitochondrion. [119] The exact number of genes encoded by the nucleus and the mitochondrial genome differs between species. Most mitochondrial genomes are circular. [120] In general, mitochondrial DNA lacks introns, as is the case in the human mitochondrial genome [119] however, introns have been observed in some eukaryotic mitochondrial DNA, [121] such as that of yeast [122] and protists, [123] including Dictyostelium discoideum. [124] Between protein-coding regions, tRNAs are present. Mitochondrial tRNA genes have different sequences from the nuclear tRNAs but lookalikes of mitochondrial tRNAs have been found in the nuclear chromosomes with high sequence similarity. [125]

In animals, the mitochondrial genome is typically a single circular chromosome that is approximately 16 kb long and has 37 genes. The genes, while highly conserved, may vary in location. Curiously, this pattern is not found in the human body louse (Pediculus humanus). Instead, this mitochondrial genome is arranged in 18 minicircular chromosomes, each of which is 3–4 kb long and has one to three genes. [126] This pattern is also found in other sucking lice, but not in chewing lice. Recombination has been shown to occur between the minichromosomes.

Alternative genetic code Edit

Exceptions to the standard genetic code in mitochondria [17]
Organism Codon Standard Mitochondria
Mammals AGA, AGG Arginine Stop codon
Invertebrates AGA, AGG Arginine Serine
Fungi CUA Leucine Threonine
All of the above AUA Isoleucine Methionine
UGA Stop codon Tryptophan

While slight variations on the standard genetic code had been predicted earlier, [127] none was discovered until 1979, when researchers studying human mitochondrial genes determined that they used an alternative code. [128] However, the mitochondria of many other eukaryotes, including most plants, use the standard code. [129] Many slight variants have been discovered since, [130] including various alternative mitochondrial codes. [131] Further, the AUA, AUC, and AUU codons are all allowable start codons.

Some of these differences should be regarded as pseudo-changes in the genetic code due to the phenomenon of RNA editing, which is common in mitochondria. In higher plants, it was thought that CGG encoded for tryptophan and not arginine however, the codon in the processed RNA was discovered to be the UGG codon, consistent with the standard genetic code for tryptophan. [132] Of note, the arthropod mitochondrial genetic code has undergone parallel evolution within a phylum, with some organisms uniquely translating AGG to lysine. [133]

Replication and inheritance Edit

Mitochondria divide by binary fission, similar to bacteria. [134] The regulation of this division differs between eukaryotes. In many single-celled eukaryotes, their growth and division are linked to the cell cycle. For example, a single mitochondrion may divide synchronously with the nucleus. This division and segregation process must be tightly controlled so that each daughter cell receives at least one mitochondrion. In other eukaryotes (in mammals for example), mitochondria may replicate their DNA and divide mainly in response to the energy needs of the cell, rather than in phase with the cell cycle. When the energy needs of a cell are high, mitochondria grow and divide. When energy use is low, mitochondria are destroyed or become inactive. In such examples mitochondria are apparently randomly distributed to the daughter cells during the division of the cytoplasm. Mitochondrial dynamics, the balance between mitochondrial fusion and fission, is an important factor in pathologies associated with several disease conditions. [135]

The hypothesis of mitochondrial binary fission has relied on the visualization by fluorescence microscopy and conventional transmission electron microscopy (TEM). The resolution of fluorescence microscopy (

200 nm) is insufficient to distinguish structural details, such as double mitochondrial membrane in mitochondrial division or even to distinguish individual mitochondria when several are close together. Conventional TEM has also some technical limitations [ which? ] in verifying mitochondrial division. Cryo-electron tomography was recently used to visualize mitochondrial division in frozen hydrated intact cells. It revealed that mitochondria divide by budding. [136]

An individual's mitochondrial genes are inherited only from the mother, with rare exceptions. [137] In humans, when an egg cell is fertilized by a sperm, the mitochondria, and therefore the mitochondrial DNA, usually come from the egg only. The sperm's mitochondria enter the egg, but do not contribute genetic information to the embryo. [138] Instead, paternal mitochondria are marked with ubiquitin to select them for later destruction inside the embryo. [139] The egg cell contains relatively few mitochondria, but these mitochondria divide to populate the cells of the adult organism. This mode is seen in most organisms, including the majority of animals. However, mitochondria in some species can sometimes be inherited paternally. This is the norm among certain coniferous plants, although not in pine trees and yews. [140] For Mytilids, paternal inheritance only occurs within males of the species. [141] [142] [143] It has been suggested that it occurs at a very low level in humans. [144]

Uniparental inheritance leads to little opportunity for genetic recombination between different lineages of mitochondria, although a single mitochondrion can contain 2–10 copies of its DNA. [118] What recombination does take place maintains genetic integrity rather than maintaining diversity. However, there are studies showing evidence of recombination in mitochondrial DNA. It is clear that the enzymes necessary for recombination are present in mammalian cells. [145] Further, evidence suggests that animal mitochondria can undergo recombination. [146] The data are more controversial in humans, although indirect evidence of recombination exists. [147] [148]

Entities undergoing uniparental inheritance and with little to no recombination may be expected to be subject to Muller's ratchet, the accumulation of deleterious mutations until functionality is lost. Animal populations of mitochondria avoid this buildup through a developmental process known as the mtDNA bottleneck. The bottleneck exploits stochastic processes in the cell to increase in the cell-to-cell variability in mutant load as an organism develops: a single egg cell with some proportion of mutant mtDNA thus produces an embryo where different cells have different mutant loads. Cell-level selection may then act to remove those cells with more mutant mtDNA, leading to a stabilisation or reduction in mutant load between generations. The mechanism underlying the bottleneck is debated, [149] [150] [151] with a recent mathematical and experimental metastudy providing evidence for a combination of random partitioning of mtDNAs at cell divisions and random turnover of mtDNA molecules within the cell. [152]

DNA repair Edit

Mitochondria can repair oxidative DNA damage by mechanisms analogous to those occurring in the cell nucleus. The proteins employed in mtDNA repair are encoded by nuclear genes, and are translocated to the mitochondria. The DNA repair pathways in mammalian mitochondria include base excision repair, double-strand break repair, direct reversal and mismatch repair. [153] [154] Also DNA damages may be bypassed, rather than repaired, by translesion synthesis.

Of the several DNA repair process in mitochondria, the base excision repair pathway has been most comprehensively studied. [154] Base excision repair is carried out by a sequence of enzymatic catalyzed steps that include recognition and excision of a damaged DNA base, removal of the resulting abasic site, end processing, gap filling and ligation. A common damage in mtDNA that is repaired by base excision repair is 8-oxoguanine produced by the oxidation of guanine. [155]

Double-strand breaks can be repaired by homologous recombinational repair in both mammalian mtDNA [156] and plant mtDNA. [157] Double-strand breaks in mtDNA can also be repaired by microhomology-mediated end joining. [158] Although there is evidence for the repair processes of direct reversal and mismatch repair in mtDNA, these processes are not well characterized. [154]

Lack of mitochondrial DNA Edit

Some organisms have lost mitochondrial DNA altogether. In these cases, genes encoded by the mitochondrial DNA have been lost or transferred to the nucleus. [117] Cryptosporidium, have mitochondria that lack any DNA, presumably because all their genes have been lost or transferred. [159] In Cryptosporidium, the mitochondria have an altered ATP generation system that renders the parasite resistant to many classical mitochondrial inhibitors such as cyanide, azide, and atovaquone. [159] Mitochondria that lack their own DNA have been found in a marine parasitic dinoflagellate from the genus Amoebophyra. This microorganism, A. cerati, has functional mitochondria that lack a genome. [160] In related species, the mitochondrial genome still has three genes, but in A. cerati only a single mitochondrial gene — the cytochrome c oxidase I gene (cox1) — is found, and it has migrated to the genome of the nucleus. [161]

The near-absence of genetic recombination in mitochondrial DNA makes it a useful source of information for studying population genetics and evolutionary biology. [162] Because all the mitochondrial DNA is inherited as a single unit, or haplotype, the relationships between mitochondrial DNA from different individuals can be represented as a gene tree. Patterns in these gene trees can be used to infer the evolutionary history of populations. The classic example of this is in human evolutionary genetics, where the molecular clock can be used to provide a recent date for mitochondrial Eve. [163] [164] This is often interpreted as strong support for a recent modern human expansion out of Africa. [165] Another human example is the sequencing of mitochondrial DNA from Neanderthal bones. The relatively large evolutionary distance between the mitochondrial DNA sequences of Neanderthals and living humans has been interpreted as evidence for the lack of interbreeding between Neanderthals and modern humans. [166]

However, mitochondrial DNA reflects only the history of the females in a population. This can be partially overcome by the use of paternal genetic sequences, such as the non-recombining region of the Y-chromosome. [165]

Recent measurements of the molecular clock for mitochondrial DNA [167] reported a value of 1 mutation every 7884 years dating back to the most recent common ancestor of humans and apes, which is consistent with estimates of mutation rates of autosomal DNA (10 −8 per base per generation). [168]

Mitochondrial diseases Edit

Damage and subsequent dysfunction in mitochondria is an important factor in a range of human diseases due to their influence in cell metabolism. Mitochondrial disorders often present as neurological disorders, including autism. [15] They can also manifest as myopathy, diabetes, multiple endocrinopathy, and a variety of other systemic disorders. [169] Diseases caused by mutation in the mtDNA include Kearns–Sayre syndrome, MELAS syndrome and Leber's hereditary optic neuropathy. [170] In the vast majority of cases, these diseases are transmitted by a female to her children, as the zygote derives its mitochondria and hence its mtDNA from the ovum. Diseases such as Kearns-Sayre syndrome, Pearson syndrome, and progressive external ophthalmoplegia are thought to be due to large-scale mtDNA rearrangements, whereas other diseases such as MELAS syndrome, Leber's hereditary optic neuropathy, MERRF syndrome, and others are due to point mutations in mtDNA. [169]

In other diseases, defects in nuclear genes lead to dysfunction of mitochondrial proteins. This is the case in Friedreich's ataxia, hereditary spastic paraplegia, and Wilson's disease. [171] These diseases are inherited in a dominance relationship, as applies to most other genetic diseases. A variety of disorders can be caused by nuclear mutations of oxidative phosphorylation enzymes, such as coenzyme Q10 deficiency and Barth syndrome. [169] Environmental influences may interact with hereditary predispositions and cause mitochondrial disease. For example, there may be a link between pesticide exposure and the later onset of Parkinson's disease. [172] [173] Other pathologies with etiology involving mitochondrial dysfunction include schizophrenia, bipolar disorder, dementia, Alzheimer's disease, [174] [175] Parkinson's disease, epilepsy, stroke, cardiovascular disease, chronic fatigue syndrome, retinitis pigmentosa, and diabetes mellitus. [176] [177]

Mitochondria-mediated oxidative stress plays a role in cardiomyopathy in type 2 diabetics. Increased fatty acid delivery to the heart increases fatty acid uptake by cardiomyocytes, resulting in increased fatty acid oxidation in these cells. This process increases the reducing equivalents available to the electron transport chain of the mitochondria, ultimately increasing reactive oxygen species (ROS) production. ROS increases uncoupling proteins (UCPs) and potentiate proton leakage through the adenine nucleotide translocator (ANT), the combination of which uncouples the mitochondria. Uncoupling then increases oxygen consumption by the mitochondria, compounding the increase in fatty acid oxidation. This creates a vicious cycle of uncoupling furthermore, even though oxygen consumption increases, ATP synthesis does not increase proportionally because the mitochondria are uncoupled. Less ATP availability ultimately results in an energy deficit presenting as reduced cardiac efficiency and contractile dysfunction. To compound the problem, impaired sarcoplasmic reticulum calcium release and reduced mitochondrial reuptake limits peak cytosolic levels of the important signaling ion during muscle contraction. Decreased intra-mitochondrial calcium concentration increases dehydrogenase activation and ATP synthesis. So in addition to lower ATP synthesis due to fatty acid oxidation, ATP synthesis is impaired by poor calcium signaling as well, causing cardiac problems for diabetics. [178]

Relationships to aging Edit

There may be some leakage of the high-energy electrons in the respiratory chain to form reactive oxygen species. This was thought to result in significant oxidative stress in the mitochondria with high mutation rates of mitochondrial DNA. [179] Hypothesized links between aging and oxidative stress are not new and were proposed in 1956, [180] which was later refined into the mitochondrial free radical theory of aging. [181] A vicious cycle was thought to occur, as oxidative stress leads to mitochondrial DNA mutations, which can lead to enzymatic abnormalities and further oxidative stress.

A number of changes can occur to mitochondria during the aging process. [182] Tissues from elderly humans show a decrease in enzymatic activity of the proteins of the respiratory chain. [183] However, mutated mtDNA can only be found in about 0.2% of very old cells. [184] Large deletions in the mitochondrial genome have been hypothesized to lead to high levels of oxidative stress and neuronal death in Parkinson's disease. [185] Mitochondrial dysfunction has also been shown to occur in amyotrophic lateral sclerosis. [186] [187]

Since mitochondria cover a pivotal role in the ovarian function, by providing ATP necessary for the development from germinal vesicle to mature oocyte, a decreased mitochondria function can lead to inflammation, resulting in premature ovarian failure and accelerated ovarian aging. The caused dysfunction is then reflected both in quantitative (such as mtDNA copy number and mtDNA deletions), qualitative (such as mutations and strand breaks) and oxidative damages (such as dysfunctional mitochondria due to ROS), which are not only relevant in ovarian aging, but perturb oocyte-cumulus crosstalk in the ovary, are linked to genetic disorders (such as Fragile X) and can interfere with embryo selection. [188]

The first observations of intracellular structures that probably represented mitochondria were published in the 1840s. [189] Richard Altmann, in 1890, established them as cell organelles and called them "bioblasts". [189] [190] In 1898, Carl Benda coined the term "mitochondria" from the Greek μίτος , mitos, "thread", and χονδρίον , chondrion, "granule". [191] [189] [192] Leonor Michaelis discovered that Janus green can be used as a supravital stain for mitochondria in 1900. In 1904, Friedrich Meves, made the first recorded observation of mitochondria in plants in cells of the white waterlily, Nymphaea alba [189] [193] and in 1908, along with Claudius Regaud, suggested that they contain proteins and lipids. Benjamin F. Kingsbury, in 1912, first related them with cell respiration, but almost exclusively based on morphological observations. [189] In 1913, particles from extracts of guinea-pig liver were linked to respiration by Otto Heinrich Warburg, which he called "grana". Warburg and Heinrich Otto Wieland, who had also postulated a similar particle mechanism, disagreed on the chemical nature of the respiration. It was not until 1925, when David Keilin discovered cytochromes, that the respiratory chain was described. [189]

In 1939, experiments using minced muscle cells demonstrated that cellular respiration using one oxygen atom can form two adenosine triphosphate (ATP) molecules, and in 1941, the concept of the phosphate bonds of ATP being a form of energy in cellular metabolism was developed by Fritz Albert Lipmann. In the following years, the mechanism behind cellular respiration was further elaborated, although its link to the mitochondria was not known. [189] The introduction of tissue fractionation by Albert Claude allowed mitochondria to be isolated from other cell fractions and biochemical analysis to be conducted on them alone. In 1946, he concluded that cytochrome oxidase and other enzymes responsible for the respiratory chain were isolated to the mitochondria. Eugene Kennedy and Albert Lehninger discovered in 1948 that mitochondria are the site of oxidative phosphorylation in eukaryotes. Over time, the fractionation method was further developed, improving the quality of the mitochondria isolated, and other elements of cell respiration were determined to occur in the mitochondria. [189]

The first high-resolution electron micrographs appeared in 1952, replacing the Janus Green stains as the preferred way to visualize mitochondria. [189] This led to a more detailed analysis of the structure of the mitochondria, including confirmation that they were surrounded by a membrane. It also showed a second membrane inside the mitochondria that folded up in ridges dividing up the inner chamber and that the size and shape of the mitochondria varied from cell to cell.

The popular term "powerhouse of the cell" was coined by Philip Siekevitz in 1957. [3]

In 1967, it was discovered that mitochondria contained ribosomes. [194] In 1968, methods were developed for mapping the mitochondrial genes, with the genetic and physical map of yeast mitochondrial DNA completed in 1976. [189]

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Where do the protons in the mitochondrial intermembrane space originally come from? - Biology

74 notecards = 19 pages ( 4 cards per page)

Campbell Biology: Chapter 10 Test Preparation (powell_h)

If photosynthesizing green algae are provided with CO₂ synthesized with heavy oxygen (¹⁸O), later analysis will show that all but one of the following compounds produced by the algae contain the ¹⁸O label. That one is
A) 3-phosphoglycerate.
B) glyceraldehyde 3-phosphate (G3P).
C) glucose.
D) ribulose bisphosphate (RuBP).
E) O₂.

Which of the following are products of the light reactions of photosynthesis that are utilized in the Calvin cycle?
A) CO₂ and glucose
B) H₂O and O₂
C) ADP, Pi, and NADP⁺
D) electrons and H⁺

Photosynthesis is not responsible for
A) oxygen in the atmosphere.
B) the ozone layer.
C) most of the organic carbon on Earth's surface.
D) atmospheric CO₂.
E) fossil fuels.

Where does the Calvin cycle take place?
A) stroma of the chloroplast
B) thylakoid membrane
C) cytoplasm surrounding the chloroplast
D) interior of the thylakoid (thylakoid space)
E) outer membrane of the chloroplast

In any ecosystem, terrestrial or aquatic, what group(s) is (are) always necessary?
A) autotrophs and heterotrophs
B) producers and primary consumers
C) photosynthesizers
D) autotrophs
E) green plants

In autotrophic bacteria, where are the enzymes located that can carry on carbon fixation (reduction of carbon dioxide to carbohydrate)?
A) in chloroplast membranes
B) in chloroplast stroma
C) in the cytosol
D) in the nucleoid
E) in the infolded plasma membrane

When oxygen is released as a result of photosynthesis, it is a direct by-product of
A) reducing NADP⁺.
B) splitting water molecules.
C) chemiosmosis.
D) the electron transfer system of photosystem I.
E) the electron transfer system of photosystem II.

A plant has a unique photosynthetic pigment. The leaves of this plant appear to be reddish yellow. What wavelengths of visible light are being absorbed by this pigment?
A) red and yellow
B) blue and violet
C) green and yellow
D) blue, green, and red
E) green, blue, and yellow

Halobacterium has a photosynthetic membrane that is colored purple. Its photosynthetic action spectrum is exactly complementary (opposite to) the action spectrum for green plants. What wavelengths of light do the Halobacterium photosynthetic pigments absorb?
A) red and yellow
B) blue, green, and red
C) green and yellow
D) red and green
E) blue and red

In the thylakoid membranes, what is the main role of the antenna pigment molecules?
A) split water and release oxygen to the reaction-center chlorophyll
B) harvest photons and transfer light energy to the reaction-center chlorophyll
C) synthesize ATP from ADP and Pi
D) transfer electrons to ferredoxin and then NADPH
E) concentrate photons within the stroma

Which of the events listed below occurs in the light reactions of photosynthesis?
A) NADP is produced.
B) NADPH is reduced to NADP⁺.
C) Carbon dioxide is incorporated into PGA.
D) ATP is phosphorylated to yield ADP.
E) Light is absorbed and funneled to reaction-center chlorophyll a.

Which statement describes the functioning of photosystem II?
A) Light energy excites electrons in the thylakoid membrane electron transport chain.
B) Photons are passed along to a reaction-center chlorophyll.
C) The P680 chlorophyll donates a pair of protons to NADP⁺, which is thus converted to NADPH.
D) The electron vacancies in P680⁺ are filled by electrons derived from water.
E) The splitting of water yields molecular carbon dioxide as a by-product.

Which of the following are directly associated with photosystem I?
A) harvesting of light energy by ATP
B) receiving electrons from the thylakoid membrane electron transport chain
C) generation of molecular oxygen
D) extraction of hydrogen electrons from the splitting of water
E) passing electrons to the thylakoid membrane electron transport chain

Some photosynthetic organisms contain chloroplasts that lack photosystem II, yet are able to survive. The best way to detect the lack of photosystem II in these organisms would be
A) to determine if they have thylakoids in the chloroplasts.
B) to test for liberation of O₂ in the light.
C) to test for CO₂ fixation in the dark.
D) to do experiments to generate an action spectrum.
E) to test for production of either sucrose or starch.

What are the products of linear photophosphorylation?
A) heat and fluorescence
B) ATP and P700
E) P700 and P680

As a research scientist, you measure the amount of ATP and NADPH consumed by the Calvin cycle in 1 hour. You find 30,000 molecules of ATP consumed, but only 20,000 molecules of NADPH. Where did the extra ATP molecules come from?
A) photosystem II
B) photosystem I
C) cyclic electron flow
D) linear electron flow
E) chlorophyll

Assume a thylakoid is somehow punctured so that the interior of the thylakoid is no longer separated from the stroma. This damage will have the most direct effect on which of the following processes?
A) the splitting of water
B) the absorption of light energy by chlorophyll
C) the flow of electrons from photosystem II to photosystem I
D) the synthesis of ATP
E) the reduction of NADP⁺

What does the chemiosmotic process in chloroplasts involve?
A) establishment of a proton gradient across the thylakoid membrane
B) diffusion of electrons through the thylakoid membrane
C) reduction of water to produce ATP energy
D) movement of water by osmosis into the thylakoid space from the stroma
E) formation of glucose, using carbon dioxide, NADPH, and ATP

Suppose the interior of the thylakoids of isolated chloroplasts were made acidic and then transferred in the dark to a pH 8 solution. What would be likely to happen?
A) The isolated chloroplasts will make ATP.
B) The Calvin cycle will be activated.
C) Cyclic photophosphorylation will occur.
D) The isolated chloroplasts will generate oxygen gas.
E) The isolated chloroplasts will reduce NADP⁺ to NADPH.

In a plant cell, where are the ATP synthase complexes located?
A) thylakoid membrane only
B) plasma membrane only
C) inner mitochondrial membrane only
D) thylakoid membrane and inner mitochondrial membrane
E) thylakoid membrane and plasma membrane

In mitochondria, chemiosmosis translocates protons from the matrix into the intermembrane space, whereas in chloroplasts, chemiosmosis translocates protons from
A) the stroma to the photosystem II.
B) the matrix to the stroma.
C) the stroma to the thylakoid space.
D) the intermembrane space to the matrix.
E) the thylakoid space to the stroma.

Which of the following statements best describes the relationship between photosynthesis and respiration?
A) Respiration runs the biochemical pathways of photosynthesis in reverse.
B) Photosynthesis stores energy in complex organic molecules, whereas respiration releases it.
C) Photosynthesis occurs only in plants and respiration occurs only in animals.
D) ATP molecules are produced in photosynthesis and used up in respiration.
E) Respiration is anabolic and photosynthesis is catabolic.

Where are the molecules of the electron transport chain found in plant cells?
A) thylakoid membranes of chloroplasts
B) stroma of chloroplasts
C) outer membrane of mitochondria
D) matrix of mitochondria
E) cytoplasm

In photosynthetic cells, synthesis of ATP by the chemiosmotic mechanism occurs during
A) photosynthesis only.
B) respiration only.
C) both photosynthesis and respiration.
D) neither photosynthesis nor respiration.
E) photorespiration only.

Reduction of oxygen to form water occurs during
A) photosynthesis only.
B) respiration only.
C) both photosynthesis and respiration.
D) neither photosynthesis nor respiration.
E) photorespiration only.

Reduction of NADP⁺ occurs during
A) photosynthesis.
B) respiration.
C) both photosynthesis and respiration.
D) neither photosynthesis nor respiration.
E) photorespiration.

The splitting of carbon dioxide to form oxygen gas and carbon compounds occurs during
A) photosynthesis.
B) respiration.
C) both photosynthesis and respiration.
D) neither photosynthesis nor respiration.
E) photorespiration.

Generation of proton gradients across membranes occurs during
A) photosynthesis.
B) respiration.
C) both photosynthesis and respiration.
D) neither photosynthesis nor respiration.
E) photorespiration.

What is the relationship between wavelength of light and the quantity of energy per photon?
A) They have a direct, linear relationship.
B) They are inversely related.
C) They are logarithmically related.
D) They are separate phenomena.
E) They are only related in certain parts of the spectrum.

P680⁺ is said to be the strongest biological oxidizing agent. Why?
A) It is the receptor for the most excited electron in either photosystem.
B) It is the molecule that transfers electrons to plastoquinone (Pq) of the electron transfer system.
C) It transfers its electrons to reduce NADP⁺ to NADPH.
D) This molecule has a stronger attraction for electrons than oxygen, to obtain electrons from water.
E) It has a positive charge.

Some photosynthetic bacteria (e.g., purple sulfur bacteria) have only photosystem I, whereas others (e.g., cyanobacteria) have both photosystem I and photosystem II. Which of the following might this observation imply?
A) Photosystem II was selected against in some species.
B) Photosynthesis with only photosystem I is more ancestral.
C) Photosystem II may have evolved to be more photoprotective.
D) Linear electron flow is more primitive than cyclic flow of electrons.
E) Cyclic flow is more necessary than linear electron flow.

electron flow may be photoprotective (protective to light-induced damage). Which of the following experiments could provide information on this phenomenon?
A) use mutated organisms that can grow but that cannot carry out cyclic flow of electrons and compare their abilities to photosynthesize in different light intensities against those of wild-type organisms
B) use plants that can carry out both linear and cyclic electron flow, or only one or another of these processes, and compare their light absorbance at different wavelengths and different light intensities
C) use bacteria that have only cyclic flow and look for their frequency of mutation damage at different light intensities
D) use bacteria with only cyclic flow and measure the number and types of photosynthetic pigments they have in their membranes
E) use plants with only photosystem I operative and measure how much damage occurs at different wavelengths

Carotenoids are often found in foods that are considered to have antioxidant properties in human nutrition. What related function do they have in plants?
A) They serve as accessory pigments to increase light absorption.
B) They protect against oxidative damage from excessive light energy.
C) They shield the sensitive chromosomes of the plant from harmful ultraviolet radiation.
D) They reflect orange light and enhance red light absorption by chlorophyll.
E) They take up and remove toxins from the groundwater.

In thylakoids, protons travel through ATP synthase from the thylakoid space to the stroma. Therefore, the catalytic "knobs" of ATP synthase would be located
A) on the side facing the thylakoid space.
B) on the ATP molecules themselves.
C) on the pigment molecules of photosystem I and photosystem II.
D) on the stromal side of the membrane.
E) built into the center of the thylakoid stack (granum).

In metabolic processes of cell respiration and photosynthesis, prosthetic groups such as heme and iron-sulfur complexes are encountered in components of the electron transport chain. What do they do?
A) donate electrons
B) act as reducing agents
C) act as oxidizing agents
D) transport protons within the mitochondria and chloroplasts
E) both oxidize and reduce during electron transport

In a cyanobacterium, the reactions that produce NADPH occur in
A) the light reactions alone.
B) the Calvin cycle alone.
C) both the light reactions and the Calvin cycle.
D) neither the light reactions nor the Calvin cycle.
E) the chloroplast, but is not part of photosynthesis.

The reactions that produce molecular oxygen (O₂) take place in
A) the light reactions alone.
B) the Calvin cycle alone.
C) both the light reactions and the Calvin cycle.
D) neither the light reactions nor the Calvin cycle.
E) the chloroplast, but are not part of photosynthesis.

The accumulation of free oxygen in Earth's atmosphere began
A) with the origin of life and respiratory metabolism.
B) with the origin of photosynthetic bacteria that had photosystem I.
C) with the origin of cyanobacteria that had both photosystem I and photosystem II.
D) with the origin of chloroplasts in photosynthetic eukaryotic algae.
E) with the origin of land plants.

A flask containing photosynthetic green algae and a control flask containing water with no algae are both placed under a bank of lights, which are set to cycle between 12 hours of light and 12 hours of dark. The dissolved oxygen concentrations in both flasks are monitored. Predict what the relative dissolved oxygen concentrations will be in the flask with algae compared to the control flask.
A) The dissolved oxygen in the flask with algae will always be higher.
B) The dissolved oxygen in the flask with algae will always be lower.
C) The dissolved oxygen in the flask with algae will be higher in the light, but the same in the dark.
D) The dissolved oxygen in the flask with algae will be higher in the light, but lower in the dark.
E) The dissolved oxygen in the flask with algae will not be different from the control flask at any time.

Where do the enzymatic reactions of the Calvin cycle take place?
A) stroma of the chloroplast
B) thylakoid membranes
C) matrix of the mitochondria
D) cytosol around the chloroplast
E) thylakoid space

What is the primary function of the Calvin cycle?
A) use ATP to release carbon dioxide
B) use NADPH to release carbon dioxide
C) split water and release oxygen
D) transport RuBP out of the chloroplast
E) synthesize simple sugars from carbon dioxide

In C₃ photosynthesis, the reactions that require ATP take place in
A) the light reactions alone.
B) the Calvin cycle alone.
C) both the light reactions and the Calvin cycle.
D) neither the light reactions nor the Calvin cycle.
E) the chloroplast, but is not part of photosynthesis.

In a plant leaf, the reactions that produce NADH occur in
A) the light reactions alone.
B) the Calvin cycle alone.
C) both the light reactions and the Calvin cycle.
D) neither the light reactions nor the Calvin cycle.
E) the chloroplast, but is not part of photosynthesis.

The NADPH required for the Calvin cycle comes from
A) reactions initiated in photosystem I.
B) reactions initiated in photosystem II.
C) the citric acid cycle.
D) glycolysis.
E) oxidative phosphorylation.

Reactions that require CO₂ take place in
A) the light reactions alone.
B) the Calvin cycle alone.
C) both the light reactions and the Calvin cycle.
D) neither the light reactions nor the Calvin cycle.
E) the chloroplast, but is not part of photosynthesis.

ap bio makes me wanna die

Which of the following statements best represents the relationships between the light reactions and the Calvin cycle?
A) The light reactions provide ATP and NADPH to the Calvin cycle, and the cycle returns ADP, Pi, and NADP⁺ to the light reactions.
B) The light reactions provide ATP and NADPH to the carbon fixation step of the Calvin cycle, and the cycle provides water and electrons to the light reactions.
C) The light reactions supply the Calvin cycle with CO₂ to produce sugars, and the Calvin cycle supplies the light reactions with sugars to produce ATP.
D) The light reactions provide the Calvin cycle with oxygen for electron flow, and the Calvin cycle provides the light reactions with water to split.
E) There is no relationship between the light reactions and the Calvin cycle.

Three "turns" of the Calvin cycle generate a "surplus" molecule of glyceraldehyde 3-phosphate (G3P). Which of the following is a consequence of this?
A) Formation of a molecule of glucose would require nine "turns."
B) G3P more readily forms sucrose and other disaccharides than it does monosaccharides.
C) Some plants would not taste sweet to us.
D) The formation of sucrose and starch in plants involves assembling G3P molecules, with or without further rearrangements.
E) Plants accumulate and store G3P.

In the process of carbon fixation, RuBP attaches a CO₂ to produce a six-carbon molecule, which is then split to produce two molecules of 3-phosphoglycerate. After phosphorylation and reduction produces glyceraldehyde 3-phosphate (G3P), what more needs to happen to complete the Calvin cycle?
A) addition of a pair of electrons from NADPH
B) inactivation of RuBP carboxylase enzyme
C) regeneration of ATP from ADP
D) regeneration of RuBP
E) regeneration of NADP⁺

The pH of the inner thylakoid space has been measured, as have the pH of the stroma and of the cytosol of a particular plant cell. Which, if any, relationship would you expect to find?
A) The pH within the thylakoid is less than that of the stroma.
B) The pH of the stroma is lower than that of the other two measurements.
C) The pH of the stroma is higher than that of the thylakoid space but lower than that of the cytosol.
D) The pH of the thylakoid space is higher than that anywhere else in the cell.
E) There is no consistent relationship.

The phylogenetic distribution of the enzyme rubisco is limited to
A) C₃ plants only.
B) C₃ and C₄ plants.
C) all photosynthetic eukaryotes.
D) all known photoautotrophs, both bacterial and eukaryotic.
E) all living cells.

Photorespiration occurs when rubisco reacts RuBP with
A) CO₂.
B) O₂.
C) glyceraldehyde 3-phosphate.
D) 3-phosphoglycerate.

In an experiment studying photosynthesis performed during the day, you provide a plant with radioactive carbon (¹⁴C) dioxide as a metabolic tracer. The ¹⁴C is incorporated first into oxaloacetate. The plant is best characterized as a
A) C₄ plant.
B) C₃ plant.
C) CAM plant.
D) heterotroph.
E) chemoautotroph.

Why are C₄ plants able to photosynthesize with no apparent photorespiration?
A) They do not participate in the Calvin cycle.
B) They use PEP carboxylase to initially fix CO₂.
C) They are adapted to cold, wet climates.
D) They conserve water more efficiently.
E) They exclude oxygen from their tissues.

CAM plants keep stomata closed in daytime, thus reducing loss of water. They can do this because they
A) fix CO₂ into organic acids during the night.
B) fix CO₂ into sugars in the bundle-sheath cells.
C) fix CO₂ into pyruvate in the mesophyll cells.
D) use the enzyme phosphofructokinase, which outcompetes rubisco for CO₂.
E) use photosystem I and photosystem II at night.

Photorespiration lowers the efficiency of photosynthesis by
A) carbon dioxide molecules.
B) 3-phosphoglycerate molecules.
C) ATP molecules.
D) ribulose bisphosphate molecules.
E) RuBP carboxylase molecules.

The alternative pathways of photosynthesis using the C₄ or CAM systems are said to be compromises. Why?
A) Each one minimizes both water loss and rate of photosynthesis.
B) C₄ compromises on water loss and CAM compromises on photorespiration.
C) Both minimize photorespiration but expend more ATP during carbon fixation.
D) CAM plants allow more water loss, while C₄ plants allow less CO₂ into the plant.
E) C₄ plants allow less water loss but CAM plants allow more water loss.

If plant gene alterations cause the plants to be deficient in photorespiration, what would most probably occur?
A) Photosynthetic efficiency would be reduced at low light intensities.
B) Cells would carry on the Calvin cycle at a much slower rate.
C) Less ATP would be generated.
D) There would be more light-induced damage to the cells.
E) Less oxygen would be produced.

Compared to C₃ plants, C₄ plants
A) can continue to fix CO₂ even at relatively low CO2 concentrations and high oxygen concentrations.
B) have higher rates of photorespiration.
C) do not use rubisco for carbon fixation.
D) grow better under cool, moist conditions.
E) make a four-carbon compound, oxaloacetate, which is then delivered to the citric acid cycle in mitochondria.

If atmospheric CO₂ concentrations increase twofold or more, how will plants be affected, disregarding any changes in climate?
A) All plants will experience increased rates of photosynthesis.
B) C₃ plants will have faster growth C₄ plants will be minimally affected.
C) C₄ plants will have faster growth C₃ plants will be minimally affected.
D) C₃ plants will have faster growth C₄ plants will have slower growth.
E) Plant growth will not be affected because atmospheric CO₂ concentrations are never limiting for plant growth.

Plants photosynthesize only in the light. Plants respire
A) in the dark only.
B) in the light only.
C) both in light and dark.
D) never–they get their ATP from photophosphorylation.
E) only when excessive light energy induces photorespiration.

A gardener is concerned that her greenhouse is getting too hot from too much light, and seeks to shade her plants with colored translucent plastic sheets. What color should she use to reduce overall light energy, but still maximize plant growth?
A) green
B) blue
C) yellow
D) orange
E) any color will work equally well

Theodor W. Engelmann illuminated a filament of algae with light that passed through a prism, thus exposing different segments of algae to different wavelengths of light. He added aerobic bacteria and then noted in which areas the bacteria congregated. He noted that the largest groups were found in the areas illuminated by the red and blue light.

What did Engelmann conclude about the congregation of bacteria in the red and blue areas?
A) Bacteria released excess carbon dioxide in these areas.
B) Bacteria congregated in these areas due to an increase in the temperature of the red and blue light.
C) Bacteria congregated in these areas because these areas had the most oxygen being released.
D) Bacteria are attracted to red and blue light and thus these wavelengths are more reactive than other wavelengths.
E) Bacteria congregated in these areas due to an increase in the temperature caused by an increase in photosynthesis.

Theodor W. Engelmann illuminated a filament of algae with light that passed through a prism, thus exposing different segments of algae to different wavelengths of light. He added aerobic bacteria and then noted in which areas the bacteria congregated. He noted that the largest groups were found in the areas illuminated by the red and blue light.

An outcome of this experiment was to help determine
A) the relationship between heterotrophic and autotrophic organisms.
B) the relationship between wavelengths of light and the rate of aerobic respiration.
C) the relationship between wavelengths of light and the amount of heat released.
D) the relationship between wavelengths of light and the rate of photosynthesis.
E) the relationship between the concentration of carbon dioxide and the rate of photosynthesis.

Theodor W. Engelmann illuminated a filament of algae with light that passed through a prism, thus exposing different segments of algae to different wavelengths of light. He added aerobic bacteria and then noted in which areas the bacteria congregated. He noted that the largest groups were found in the areas illuminated by the red and blue light.

If you ran the same experiment without passing light through a prism, what would you predict?
A) There would be no difference in results.
B) The bacteria would be relatively evenly distributed along the algal filaments.
C) The number of bacteria present would decrease due to an increase in the carbon dioxide concentration.
D) The number of bacteria present would increase due to an increase in the carbon dioxide concentration.
E) The number of bacteria would decrease due to a decrease in the temperature of the water.

A spaceship is designed to support animal life for a multiyear voyage to the outer planets of the solar system. Plants will be grown to provide oxygen and to recycle carbon dioxide.

Since the spaceship will be too far from the sun for photosynthesis, an artificial light source will be needed. What wavelengths of light should be used to maximize plant growth with a minimum of energy expenditure?
A) full-spectrum white light
B) green light
C) a mixture of blue and red light
D) yellow light
E) UV light

A spaceship is designed to support animal life for a multiyear voyage to the outer planets of the solar system. Plants will be grown to provide oxygen and to recycle carbon dioxide.

If the power fails and the lights go dark, what will happen to CO₂ levels?
A) CO₂ will rise as a result of both animal and plant respiration.
B) CO₂ will rise as a result of animal respiration only.
C) CO₂ will remain balanced because plants will continue to fix CO₂ in the dark.
D) CO₂ will fall because plants will increase CO₂ fixation.
E) CO₂ will fall because plants will cease to respire in the dark.

The light reactions of photosynthesis supply the Calvin cycle with
A) light energy.
B) CO₂ and ATP.
C) H₂O and NADPH.
E) sugar and O₂.

Inducible Proton Conductance

UCPs catalyze proton conductance that is controlled on multiple levels: molecular, transcriptional, translational, and proteolytic (17). They are increasingly implicated in a variety of pathophysiological processes including obesity, Type 2 diabetes mellitus, the immune response, cancer, cardiovascular disease, and age-related disease caused by oxidative stress.

Studies into the bioenergetics and inner membrane composition of brown adipose tissue mitochondria led to the discovery of UCP1 (91, 131, 153, 155, 156, 175, 176), which dissipates Δp to generate heat in mammals during non-shivering thermogenesis (47).


The complex Edit

The complex is a large integral membrane protein composed of several metal prosthetic sites and 14 [2] protein subunits in mammals. In mammals, eleven subunits are nuclear in origin, and three are synthesized in the mitochondria. The complex contains two hemes, a cytochrome a and cytochrome a3, and two copper centers, the CuA and CuB centers. [3] In fact, the cytochrome a3 and CuB form a binuclear center that is the site of oxygen reduction. Cytochrome c, which is reduced by the preceding component of the respiratory chain (cytochrome bc1 complex, complex III), docks near the CuA binuclear center and passes an electron to it, being oxidized back to cytochrome c containing Fe 3+ . The reduced CuA binuclear center now passes an electron on to cytochrome a, which in turn passes an electron on to the cytochrome a3-CuB binuclear center. The two metal ions in this binuclear center are 4.5 Å apart and coordinate a hydroxide ion in the fully oxidized state.

Crystallographic studies of cytochrome c oxidase show an unusual post-translational modification, linking C6 of Tyr(244) and the ε-N of His(240) (bovine enzyme numbering). It plays a vital role in enabling the cytochrome a3- CuB binuclear center to accept four electrons in reducing molecular oxygen to water. The mechanism of reduction was formerly thought to involve a peroxide intermediate, which was believed to lead to superoxide production. However, the currently accepted mechanism involves a rapid four-electron reduction involving immediate oxygen-oxygen bond cleavage, avoiding any intermediate likely to form superoxide. [4] : 865–866

The conserved subunits Edit

Table of conserved subunits of cytochrome c oxidase complex [5] [6]
No. Subunit name Human protein Protein description from UniProt Pfam family with Human protein
1 Cox1 COX1_HUMAN Cytochrome c oxidase subunit 1 Pfam PF00115
2 Cox2 COX2_HUMAN Cytochrome c oxidase subunit 2 Pfam PF02790, Pfam PF00116
3 Cox3 COX3_HUMAN Cytochrome c oxidase subunit 3 Pfam PF00510
4 Cox4i1 COX41_HUMAN Cytochrome c oxidase subunit 4 isoform 1, mitochondrial Pfam PF02936
5 Cox4a2 COX42_HUMAN Cytochrome c oxidase subunit 4 isoform 2, mitochondrial Pfam PF02936
6 Cox5a COX5A_HUMAN Cytochrome c oxidase subunit 5A, mitochondrial Pfam PF02284
7 Cox5b COX5B_HUMAN Cytochrome c oxidase subunit 5B, mitochondrial Pfam PF01215
8 Cox6a1 CX6A1_HUMAN Cytochrome c oxidase subunit 6A1, mitochondrial Pfam PF02046
9 Cox6a2 CX6A2_HUMAN Cytochrome c oxidase subunit 6A2, mitochondrial Pfam PF02046
10 Cox6b1 CX6B1_HUMAN Cytochrome c oxidase subunit 6B1 Pfam PF02297
11 Cox6b2 CX6B2_HUMAN Cytochrome c oxidase subunit 6B2 Pfam PF02297
12 Cox6c COX6C_HUMAN Cytochrome c oxidase subunit 6C Pfam PF02937
13 Cox7a1 CX7A1_HUMAN Cytochrome c oxidase subunit 7A1, mitochondrial Pfam PF02238
14 Cox7a2 CX7A2_HUMAN Cytochrome c oxidase subunit 7A2, mitochondrial Pfam PF02238
15 Cox7a3 COX7S_HUMAN Putative cytochrome c oxidase subunit 7A3, mitochondrial Pfam PF02238
16 Cox7b COX7B_HUMAN Cytochrome c oxidase subunit 7B, mitochondrial Pfam PF05392
17 Cox7c COX7C_HUMAN Cytochrome c oxidase subunit 7C, mitochondrial Pfam PF02935
18 Cox7r COX7R_HUMAN Cytochrome c oxidase subunit 7A-related protein, mitochondrial Pfam PF02238
19 Cox8a COX8A_HUMAN Cytochrome c oxidase subunit 8A, mitochondrial P Pfam PF02285
20 Cox8c COX8C_HUMAN Cytochrome c oxidase subunit 8C, mitochondrial Pfam PF02285
Assembly subunits [7] [8] [9]
1 Coa1 COA1_HUMAN Cytochrome c oxidase assembly factor 1 homolog Pfam PF08695
2 Coa3 COA3_HUMAN Cytochrome c oxidase assembly factor 3 homolog, mitochondrial Pfam PF09813
3 Coa4 COA4_HUMAN Cytochrome c oxidase assembly factor 4 homolog, mitochondrial Pfam PF06747
4 Coa5 COA5_HUMAN Cytochrome c oxidase assembly factor 5 Pfam PF10203
5 Coa6 COA6_HUMAN Cytochrome c oxidase assembly factor 6 homolog Pfam PF02297
6 Coa7 COA7_HUMAN Cytochrome c oxidase assembly factor 7, Pfam PF08238
7 Cox11 COX11_HUMAN Cytochrome c oxidase assembly protein COX11 mitochondrial Pfam PF04442
8 Cox14 COX14_HUMAN Cytochrome c oxidase assembly protein Pfam PF14880
9 Cox15 COX15_HUMAN Cytochrome c oxidase assembly protein COX15 homolog Pfam PF02628
10 Cox16 COX16_HUMAN Cytochrome c oxidase assembly protein COX16 homolog mitochondrial Pfam PF14138
11 Cox17 COX17_HUMAN Cytochrome c oxidase copper chaperone Pfam PF05051
12 Cox18 [10] COX18_HUMAN Mitochondrial inner membrane protein (Cytochrome c oxidase assembly protein 18) Pfam PF02096
13 Cox19 COX19_HUMAN Cytochrome c oxidase assembly protein Pfam PF06747
14 Cox20 COX20_HUMAN Cytochrome c oxidase protein 20 homolog Pfam PF12597

COX assembly in yeast is a complex process that is not entirely understood due to the rapid and irreversible aggregation of hydrophobic subunits that form the holoenzyme complex, as well as aggregation of mutant subunits with exposed hydrophobic patches. [11] COX subunits are encoded in both the nuclear and mitochondrial genomes. The three subunits that form the COX catalytic core are encoded in the mitochondrial genome.

Hemes and cofactors are inserted into subunits I & II. The two heme molecules reside in subunit I, helping with transport to subunit II where two copper molecules aid with the continued transfer of electrons. [12] Subunits I and IV initiate assembly. Different subunits may associate to form sub-complex intermediates that later bind to other subunits to form the COX complex. [11] In post-assembly modifications, COX will form a homodimer. This is required for activity. Both dimers are connected by a cardiolipin molecule, [11] [13] [14] which has been found to play a key role in stabilization of the holoenzyme complex. The dissociation of subunits VIIa and III in conjunction with the removal of cardiolipin results in total loss of enzyme activity. [14] Subunits encoded in the nuclear genome are known to play a role in enzyme dimerization and stability. Mutations to these subunits eliminate COX function. [11]

Assembly is known to occur in at least three distinct rate-determining steps. The products of these steps have been found, though specific subunit compositions have not been determined. [11]

Synthesis and assembly of COX subunits I, II, and III are facilitated by translational activators, which interact with the 5’ untranslated regions of mitochondrial mRNA transcripts. Translational activators are encoded in the nucleus. They can operate through either direct or indirect interaction with other components of translation machinery, but exact molecular mechanisms are unclear due to difficulties associated with synthesizing translation machinery in-vitro. [15] [16] Though the interactions between subunits I, II, and III encoded within the mitochondrial genome make a lesser contribution to enzyme stability than interactions between bigenomic subunits, these subunits are more conserved, indicating potential unexplored roles for enzyme activity. [17]

4 Fe 2+ -cytochrome c + 4 H + in + O2 → 4 Fe 3+ -cytochrome c + 2 H2O + 4 H + out

Two electrons are passed from two cytochrome c's, through the CuA and cytochrome a sites to the cytochrome a3- CuB binuclear center, reducing the metals to the Fe 2+ form and Cu + . The hydroxide ligand is protonated and lost as water, creating a void between the metals that is filled by O2. The oxygen is rapidly reduced, with two electrons coming from the Fe 2+ cytochrome a3, which is converted to the ferryl oxo form (Fe 4+ =O). The oxygen atom close to CuB picks up one electron from Cu + , and a second electron and a proton from the hydroxyl of Tyr(244), which becomes a tyrosyl radical. The second oxygen is converted to a hydroxide ion by picking up two electrons and a proton. A third electron arising from another cytochrome c is passed through the first two electron carriers to the cytochrome a3- CuB binuclear center, and this electron and two protons convert the tyrosyl radical back to Tyr, and the hydroxide bound to CuB 2+ to a water molecule. The fourth electron from another cytochrome c flows through CuA and cytochrome a to the cytochrome a3- CuB binuclear center, reducing the Fe 4+ =O to Fe 3+ , with the oxygen atom picking up a proton simultaneously, regenerating this oxygen as a hydroxide ion coordinated in the middle of the cytochrome a3- CuB center as it was at the start of this cycle. The net process is that four reduced cytochrome c's are used, along with 4 protons, to reduce O2 to two water molecules. [4] : 841–5

COX exists in three conformational states: fully oxidized (pulsed), partially reduced, and fully reduced. Each inhibitor has a high affinity to a different state. In the pulsed state, both the heme a3 and the CuB nuclear centers are oxidized this is the conformation of the enzyme that has the highest activity. A two-electron reduction initiates a conformational change that allows oxygen to bind at the active site to the partially-reduced enzyme. Four electrons bind to COX to fully reduce the enzyme. Its fully reduced state, which consists of a reduced Fe 2+ at the cytochrome a3 heme group and a reduced CuB + binuclear center, is considered the inactive or resting state of the enzyme. [18]

Cyanide, azide, and carbon monoxide [19] all bind to cytochrome c oxidase, inhibiting the protein from functioning and leading to the chemical asphyxiation of cells. Higher concentrations of molecular oxygen are needed to compensate for increasing inhibitor concentrations, leading to an overall reduction in metabolic activity in the cell in the presence of an inhibitor. Other ligands, such as nitric oxide and hydrogen sulfide, can also inhibit COX by binding to regulatory sites on the enzyme, reducing the rate of cellular respiration. [20]

Cyanide is a non-competitive inhibitor for COX, [21] [22] binding with high affinity to the partially-reduced state of the enzyme and hindering further reduction of the enzyme. In the pulsed state, cyanide binds slowly, but with high affinity. The ligand is posited to electrostatically stabilize both metals at once by positioning itself between them. A high nitric oxide concentration, such as one added exogenously to the enzyme, reverses cyanide inhibition of COX. [23]

Nitric oxide can reversibly [24] bind to either metal ion in the binuclear center to be oxidized to nitrite. NO and CN − will compete with oxygen to bind at the site, reducing the rate of cellular respiration. Endogenous NO, however, which is produced at lower levels, augments CN − inhibition. Higher levels of NO, which correlate with the existence of more enzyme in the reduced state, lead to a greater inhibition of cyanide. [18] At these basal concentrations, NO inhibition of Complex IV is known to have beneficial effects, such as increasing oxygen levels in blood vessel tissues. The inability of the enzyme to reduce oxygen to water results in a buildup of oxygen, which can diffuse deeper into surrounding tissues. [24] NO inhibition of Complex IV has a larger effect at lower oxygen concentrations, increasing its utility as a vasodilator in tissues of need. [24]

Hydrogen sulfide will bind COX in a noncompetitive fashion at a regulatory site on the enzyme, similar to carbon monoxide. Sulfide has the highest affinity to either the pulsed or partially reduced states of the enzyme, and is capable of partially reducing the enzyme at the heme a3 center. It is unclear whether endogenous H2S levels are sufficient to inhibit the enzyme. There is no interaction between hydrogen sulfide and the fully reduced conformation of COX. [20]

Methanol in methylated spirits is converted into formic acid, which also inhibits the same oxidase system. High levels of ATP can allosterically inhibit cytochrome c oxidase, binding from within the mitochondrial matrix. [25]

Cytochrome c oxidase has 3 subunits which are encoded by mitochondrial DNA (cytochrome c oxidase subunit I, subunit II, and subunit III). Of these 3 subunits encoded by mitochondrial DNA, two have been identified in extramitochondrial locations. In pancreatic acinar tissue, these subunits were found in zymogen granules. Additionally, in the anterior pituitary, relatively high amounts of these subunits were found in growth hormone secretory granules. [26] The extramitochondrial function of these cytochrome c oxidase subunits has not yet been characterized. Besides cytochrome c oxidase subunits, extramitochondrial localization has also been observed for large numbers of other mitochondrial proteins. [27] [28] This raises the possibility about existence of yet unidentified specific mechanisms for protein translocation from mitochondria to other cellular destinations. [26] [28] [29]

Defects involving genetic mutations altering cytochrome c oxidase (COX) functionality or structure can result in severe, often fatal metabolic disorders. Such disorders usually manifest in early childhood and affect predominantly tissues with high energy demands (brain, heart, muscle). Among the many classified mitochondrial diseases, those involving dysfunctional COX assembly are thought to be the most severe. [30]

The vast majority of COX disorders are linked to mutations in nuclear-encoded proteins referred to as assembly factors, or assembly proteins. These assembly factors contribute to COX structure and functionality, and are involved in several essential processes, including transcription and translation of mitochondrion-encoded subunits, processing of preproteins and membrane insertion, and cofactor biosynthesis and incorporation. [31]

Currently, mutations have been identified in seven COX assembly factors: SURF1, SCO1, SCO2, COX10, COX15, COX20, COA5 and LRPPRC. Mutations in these proteins can result in altered functionality of sub-complex assembly, copper transport, or translational regulation. Each gene mutation is associated with the etiology of a specific disease, with some having implications in multiple disorders. Disorders involving dysfunctional COX assembly via gene mutations include Leigh syndrome, cardiomyopathy, leukodystrophy, anemia, and sensorineural deafness.

The increased reliance of neurons on oxidative phosphorylation for energy [32] facilitates the use of COX histochemistry in mapping regional brain metabolism in animals, since it establishes a direct and positive correlation between enzyme activity and neuronal activity. [33] This can be seen in the correlation between COX enzyme amount and activity, which indicates the regulation of COX at the level of gene expression. COX distribution is inconsistent across different regions of the animal brain, but its pattern of its distribution is consistent across animals. This pattern has been observed in the monkey, mouse, and calf brain. One isozyme of COX has been consistently detected in histochemical analysis of the brain. [34]

Such brain mapping has been accomplished in spontaneous mutant mice with cerebellar disease such as reeler [35] and a transgenic model of Alzheimer's disease. [36] This technique has also been used to map learning activity in animal brain. [37]

Cellular proliferation regulation

The relationship between cellular proliferation and mitochondria has been investigated using cervical cancer HeLa cells. Tumor cells require an ample amount of ATP (Adenosine triphosphate) in order to synthesize bioactive compounds such as lipids, proteins, and nucleotides for rapid cell proliferation. The majority of ATP in tumor cells is generated via the oxidative phosphorylation pathway (OxPhos). Interference with OxPhos have shown to cause cell cycle arrest suggesting that mitochondria play a role in cell proliferation. Mitochondrial ATP production is also vital for cell division and differentiation in infection in addition to basic functions in the cell including the regulation of cell volume, solute concentration, and cellular architecture. ATP levels differ at various stages of the cell cycle suggesting that there is a relationship between the abundance of ATP and the cell's ability to enter a new cell cycle. ATP's role in the basic functions of the cell make the cell cycle sensitive to changes in the availability of mitochondrial derived ATP. The variation in ATP levels at different stages of the cell cycle support the hypothesis that mitochondria play an important role in cell cycle regulation. Although the specific mechanisms between mitochondria and the cell cycle regulation is not well understood, studies have shown that low energy cell cycle checkpoints monitor the energy capability before committing to another round of cell division.


Most eukaryotic cells have mitochondria, which produce ATP from products of the citric acid cycle, fatty acid oxidation, and amino acid oxidation. At the inner mitochondrial membrane, electrons from NADH and FADH2 pass through the electron transport chain to oxygen, which is reduced to water. [3] The electron transport chain comprises an enzymatic series of electron donors and acceptors. Each electron donor will pass electrons to a more electronegative acceptor, which in turn donates these electrons to another acceptor, a process that continues down the series until electrons are passed to oxygen, the most electronegative and terminal electron acceptor in the chain. Passage of electrons between donor and acceptor releases energy, which is used to generate a proton gradient across the mitochondrial membrane by "pumping" protons into the intermembrane space, producing a thermodynamic state that has the potential to do work. This entire process is called oxidative phosphorylation since ADP is phosphorylated to ATP by using the electrochemical gradient established by the redox reactions of the electron transport chain.

Mitochondrial redox carriers Edit

Energy obtained through the transfer of electrons down the electron transport chain is used to pump protons from the mitochondrial matrix into the intermembrane space, creating an electrochemical proton gradient (ΔpH) across the inner mitochondrial membrane. This proton gradient is largely but not exclusively responsible for the mitochondrial membrane potential (ΔΨM). [4] It allows ATP synthase to use the flow of H + through the enzyme back into the matrix to generate ATP from adenosine diphosphate (ADP) and inorganic phosphate. Complex I (NADH coenzyme Q reductase labeled I) accepts electrons from the Krebs cycle electron carrier nicotinamide adenine dinucleotide (NADH), and passes them to coenzyme Q (ubiquinone labeled Q), which also receives electrons from complex II (succinate dehydrogenase labeled II). Q passes electrons to complex III (cytochrome bc1 complex labeled III), which passes them to cytochrome c (cyt c). Cyt c passes electrons to complex IV (cytochrome c oxidase labeled IV), which uses the electrons and hydrogen ions to reduce molecular oxygen to water.

Four membrane-bound complexes have been identified in mitochondria. Each is an extremely complex transmembrane structure that is embedded in the inner membrane. Three of them are proton pumps. The structures are electrically connected by lipid-soluble electron carriers and water-soluble electron carriers. The overall electron transport chain:

Complex I Edit

In complex I (NADH ubiquinone oxireductase, Type I NADH dehydrogenase, or mitochondrial complex I EC, two electrons are removed from NADH and transferred to a lipid-soluble carrier, ubiquinone (Q). The reduced product, ubiquinol (QH2), freely diffuses within the membrane, and Complex I translocates four protons (H + ) across the membrane, thus producing a proton gradient. Complex I is one of the main sites at which premature electron leakage to oxygen occurs, thus being one of the main sites of production of superoxide. [5]

The pathway of electrons is as follows:

NADH is oxidized to NAD + , by reducing Flavin mononucleotide to FMNH2 in one two-electron step. FMNH2 is then oxidized in two one-electron steps, through a semiquinone intermediate. Each electron thus transfers from the FMNH2 to an Fe-S cluster, from the Fe-S cluster to ubiquinone (Q). Transfer of the first electron results in the free-radical (semiquinone) form of Q, and transfer of the second electron reduces the semiquinone form to the ubiquinol form, QH2. During this process, four protons are translocated from the mitochondrial matrix to the intermembrane space. [6] As the electrons become continuously oxidized and reduced throughout the complex an electron current is produced along the 180 Angstrom width of the complex within the membrane. This current powers the active transport of four protons to the intermembrane space per two electrons from NADH. [7]

Complex II Edit

In complex II (succinate dehydrogenase or succinate-CoQ reductase EC additional electrons are delivered into the quinone pool (Q) originating from succinate and transferred (via flavin adenine dinucleotide (FAD)) to Q. Complex II consists of four protein subunits: succinate dehydrogenase, (SDHA) succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial, (SDHB) succinate dehydrogenase complex subunit C, (SDHC) and succinate dehydrogenase complex, subunit D, (SDHD). Other electron donors (e.g., fatty acids and glycerol 3-phosphate) also direct electrons into Q (via FAD). Complex II is a parallel electron transport pathway to complex 1, but unlike complex 1, no protons are transported to the intermembrane space in this pathway. Therefore, the pathway through complex II contributes less energy to the overall electron transport chain process.

Complex III Edit

In complex III (cytochrome bc1 complex or CoQH2-cytochrome c reductase EC, the Q-cycle contributes to the proton gradient by an asymmetric absorption/release of protons. Two electrons are removed from QH2 at the QO site and sequentially transferred to two molecules of cytochrome c, a water-soluble electron carrier located within the intermembrane space. The two other electrons sequentially pass across the protein to the Qi site where the quinone part of ubiquinone is reduced to quinol. A proton gradient is formed by one quinol ( 2 H 2 + e − >> ) oxidations at the Qo site to form one quinone ( 2 H 2 + e − >> ) at the Qi site. (In total, four protons are translocated: two protons reduce quinone to quinol and two protons are released from two ubiquinol molecules.)

When electron transfer is reduced (by a high membrane potential or respiratory inhibitors such as antimycin A), Complex III may leak electrons to molecular oxygen, resulting in superoxide formation.

This complex is inhibited by dimercaprol (British Antilewisite, BAL), Napthoquinone and Antimycin.

Complex IV Edit

In complex IV (cytochrome c oxidase EC, sometimes called cytochrome AA3, four electrons are removed from four molecules of cytochrome c and transferred to molecular oxygen (O2), producing two molecules of water. The complex contains coordinated copper ions and several heme groups. At the same time, eight protons are removed from the mitochondrial matrix (although only four are translocated across the membrane), contributing to the proton gradient. The exact details of proton pumping in complex IV are still under study. [8] Cyanide is an inhibitor of complex 4.

Coupling with oxidative phosphorylation Edit

The chemiosmotic coupling hypothesis, proposed by Nobel Prize in Chemistry winner Peter D. Mitchell, the electron transport chain and oxidative phosphorylation are coupled by a proton gradient across the inner mitochondrial membrane. The efflux of protons from the mitochondrial matrix creates an electrochemical gradient (proton gradient). This gradient is used by the FOF1 ATP synthase complex to make ATP via oxidative phosphorylation. ATP synthase is sometimes described as Complex V of the electron transport chain. [9] The FO component of ATP synthase acts as an ion channel that provides for a proton flux back into the mitochondrial matrix. It is composed of a, b and c subunits. Protons in the inter-membranous space of mitochondria first enters the ATP synthase complex through a subunit channel. Then protons move to the c subunits. [10] The number of c subunits it has determines how many protons it will require to make the FO turn one full revolution. For example, in humans, there are 8 c subunits, thus 8 protons are required. [11] After c subunits, protons finally enters matrix using a subunit channel that opens into the mitochondrial matrix. [10] This reflux releases free energy produced during the generation of the oxidized forms of the electron carriers (NAD + and Q). The free energy is used to drive ATP synthesis, catalyzed by the F1 component of the complex. [12]
Coupling with oxidative phosphorylation is a key step for ATP production. However, in specific cases, uncoupling the two processes may be biologically useful. The uncoupling protein, thermogenin—present in the inner mitochondrial membrane of brown adipose tissue—provides for an alternative flow of protons back to the inner mitochondrial matrix. Thyroxine is also a natural uncoupler. This alternative flow results in thermogenesis rather than ATP production. [13]

Reverse electron flow Edit

Reverse electron flow, is the transfer of electrons through the electron transport chain through the reverse redox reactions. Usually requiring a significant amount of energy to be used, this can result in reducing the oxidised form of electron donors. For example, NAD+ can be reduced to NADH by complex I. [14] There are several factors that have been shown to induce reverse electron flow. However, more work needs to be done to confirm this. One such example is blockage of ATP production by ATP synthase, resulting in a build-up of protons and therefore a higher proton-motive force, inducing reverse electron flow. [15]

In eukaryotes, NADH is the most important electron donor. The associated electron transport chain is

NADHComplex IQComplex IIIcytochrome cComplex IVO2 where Complexes I, III and IV are proton pumps, while Q and cytochrome c are mobile electron carriers. The electron acceptor is molecular oxygen.

In prokaryotes (bacteria and archaea) the situation is more complicated, because there are several different electron donors and several different electron acceptors. The generalized electron transport chain in bacteria is:

Electrons can enter the chain at three levels: at the level of a dehydrogenase, at the level of the quinone pool, or at the level of a mobile cytochrome electron carrier. These levels correspond to successively more positive redox potentials, or to successively decreased potential differences relative to the terminal electron acceptor. In other words, they correspond to successively smaller Gibbs free energy changes for the overall redox reaction Donor → Acceptor.

Individual bacteria use multiple electron transport chains, often simultaneously. Bacteria can use a number of different electron donors, a number of different dehydrogenases, a number of different oxidases and reductases, and a number of different electron acceptors. For example, E. coli (when growing aerobically using glucose as an energy source) uses two different NADH dehydrogenases and two different quinol oxidases, for a total of four different electron transport chains operating simultaneously.

A common feature of all electron transport chains is the presence of a proton pump to create an electrochemical gradient over a membrane. Bacterial electron transport chains may contain as many as three proton pumps, like mitochondria, or they may contain only one or two. They always contain at least one proton pump.

Electron donors Edit

In the present day biosphere, the most common electron donors are organic molecules. Organisms that use organic molecules as an electron source are called organotrophs. Organotrophs (animals, fungi, protists) and phototrophs (plants and algae) constitute the vast majority of all familiar life forms.

Some prokaryotes can use inorganic matter as an energy source. Such an organism is called a lithotroph ("rock-eater"). Inorganic electron donors include hydrogen, carbon monoxide, ammonia, nitrite, sulfur, sulfide, manganese oxide, and ferrous iron. Lithotrophs have been found growing in rock formations thousands of meters below the surface of Earth. Because of their volume of distribution, lithotrophs may actually outnumber organotrophs and phototrophs in our biosphere.

The use of inorganic electron donors as an energy source is of particular interest in the study of evolution. This type of metabolism must logically have preceded the use of organic molecules as an energy source.

Complex I and II Edit

Bacteria can use a number of different electron donors. When organic matter is the energy source, the donor may be NADH or succinate, in which case electrons enter the electron transport chain via NADH dehydrogenase (similar to Complex I in mitochondria) or succinate dehydrogenase (similar to Complex II). Other dehydrogenases may be used to process different energy sources: formate dehydrogenase, lactate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, H2 dehydrogenase (hydrogenase), electron transport chain. Some dehydrogenases are also proton pumps others funnel electrons into the quinone pool. Most dehydrogenases show induced expression in the bacterial cell in response to metabolic needs triggered by the environment in which the cells grow. In the case of lactate dehydrogenase in E.coli, the enzyme is used aerobically and in combination with other dehydrogenases. It is inducible and is expressed when there is high concentration of DL- lactate present in the cell. [ citation needed ]

Quinone carriers Edit

Quinones are mobile, lipid-soluble carriers that shuttle electrons (and protons) between large, relatively immobile macromolecular complexes embedded in the membrane. Bacteria use ubiquinone (Coenzyme Q, the same quinone that mitochondria use) and related quinones such as menaquinone (Vitamin K2). Archaea in the genus Sulfolobus use caldariellaquinone. [16] The use of different quinones is due to slightly altered redox potentials. These changes in redox potential are caused by changes in structure of quinone. The Change in redox potentials of these quinones may be suited to changes in the electron acceptors or variations of redox potentials in bacterial complexes. [17]

Proton pumps Edit

A proton pump is any process that creates a proton gradient across a membrane. Protons can be physically moved across a membrane this is seen in mitochondrial Complexes I and IV. The same effect can be produced by moving electrons in the opposite direction. The result is the disappearance of a proton from the cytoplasm and the appearance of a proton in the periplasm. Mitochondrial Complex III uses this second type of proton pump, which is mediated by a quinone (the Q cycle).

Some dehydrogenases are proton pumps others are not. Most oxidases and reductases are proton pumps, but some are not. Cytochrome bc1 is a proton pump found in many, but not all, bacteria (it is not found in E. coli). As the name implies, bacterial bc1 is similar to mitochondrial bc1 (Complex III).

Cytochrome electron carriers Edit

Cytochromes are pigments that contain iron. They are found in two very different environments.

Some cytochromes are water-soluble carriers that shuttle electrons to and from large, immobile macromolecular structures imbedded in the membrane. The mobile cytochrome electron carrier in mitochondria is cytochrome c. Bacteria use a number of different mobile cytochrome electron carriers.

Other cytochromes are found within macromolecules such as Complex III and Complex IV. They also function as electron carriers, but in a very different, intramolecular, solid-state environment.

Electrons may enter an electron transport chain at the level of a mobile cytochrome or quinone carrier. For example, electrons from inorganic electron donors (nitrite, ferrous iron, electron transport chain.) enter the electron transport chain at the cytochrome level. When electrons enter at a redox level greater than NADH, the electron transport chain must operate in reverse to produce this necessary, higher-energy molecule.

Terminal oxidases and reductases Edit

When bacteria grow in aerobic environments, the terminal electron acceptor (O2) is reduced to water by an enzyme called an oxidase. When bacteria grow in anaerobic environments, the terminal electron acceptor is reduced by an enzyme called a reductase. In mitochondria the terminal membrane complex (Complex IV) is cytochrome oxidase. Aerobic bacteria use a number of different terminal oxidases. For example, E. coli (a facultative anaerobe) does not have a cytochrome oxidase or a bc1 complex. Under aerobic conditions, it uses two different terminal quinol oxidases (both proton pumps) to reduce oxygen to water.

Bacterial Complex IV can be split into classes according to the molecules act as terminal electron acceptors. Class I oxidases are cytochrome oxidases and use oxygen as the terminal electron acceptor. Class II oxidases are Quinol oxidases and can use a variety of terminal electron acceptors. Both of these classes can be subdivided into categories based on what redox active components they contain. E.g. Heme aa3 Class 1 terminal oxidases are much more efficient than Class 2 terminal oxidases [1]

Anaerobic bacteria, which do not use oxygen as a terminal electron acceptor, have terminal reductases individualized to their terminal acceptor. For example, E. coli can use fumarate reductase, nitrate reductase, nitrite reductase, DMSO reductase, or trimethylamine-N-oxide reductase, depending on the availability of these acceptors in the environment.

Most terminal oxidases and reductases are inducible. They are synthesized by the organism as needed, in response to specific environmental conditions.

Electron acceptors Edit

Just as there are a number of different electron donors (organic matter in organotrophs, inorganic matter in lithotrophs), there are a number of different electron acceptors, both organic and inorganic. In aerobic bacteria and facultative anaerobes if oxygen is available, it is invariably used as the terminal electron acceptor, because it generates the greatest Gibbs free energy change and produces the most energy. [18]

In anaerobic environments, different electron acceptors are used, including nitrate, nitrite, ferric iron, sulfate, carbon dioxide, and small organic molecules such as fumarate.

In oxidative phosphorylation, electrons are transferred from a low-energy electron donor such as NADH to an acceptor such as O2) through an electron transport chain. In photophosphorylation, the energy of sunlight is used to create a high-energy electron donor which can subsequently reduce redox active components. These components are then coupled to ATP synthesis via proton translocation by the electron transport chain. [8]

Photosynthetic electron transport chains, like the mitochondrial chain, can be considered as a special case of the bacterial systems. They use mobile, lipid-soluble quinone carriers (phylloquinone and plastoquinone) and mobile, water-soluble carriers (cytochromes, electron transport chain.). They also contain a proton pump. The proton pump in all photosynthetic chains resembles mitochondrial Complex III. The commonly-held theory of symbiogenesis believes that both organelles descended from bacteria.

Oxidation of metabolites liberates energy that is used to synthesize ATP in mitochondria, this is performed by the respiratory chain, which generates a proton gradient across the inner membrane to drive ATP production by the F1F0-ATP synthase.

Membrane-bound machinery that facilitates the insertion of precursor proteins into the lipid phase of a membrane, such as the oxidase assembly (OXA) insertase of the mitochondrial inner membrane.

Mitochondrial contact site and cristae organizing system

(MICOS). A large protein complex of the inner membrane with a dual role: maintenance of the cristae architecture of the inner membrane and the formation of contact sites between the inner and the outer membranes.

The translocase of the outer membrane (TOM) is a protein complex that forms the major mitochondrial entry site for precursor proteins synthesized in the cytosol.

(Hsp70). A large family of ATP-dependent molecular chaperones of

70 kDa that bind loosely folded proteins and prevent their misfolding or aggregation. The major mitochondrial heat shock protein 70 (mtHsp70) has a dual role in driving ATP-dependent protein import into the matrix and assisting in folding of proteins.

A pathway in which the amino-terminal amino acid residue links proteins to regulated proteolysis. A destabilizing residue promotes rapid degradation, whereas a stabilizing residue leads to a longer half-life of a protein.

The sorting and assembly machinery (SAM) inserts β-barrel proteins into the mitochondrial outer membrane it is also known as topogenesis of outer membrane β-barrel proteins (TOB).

Mitochondrial unfolded protein response

(UPRmt). A stress response induced by mitochondrial dysfunction that upregulates the transcription of nuclear genes encoding mitochondrial chaperones, proteases and further components that support mitochondrial recovery and survival.

Large supercomplexes in the mitochondrial inner membrane consisting of complexes I, III and IV of the respiratory chain.

The mitochondrial inner membrane consists of two domains: the folded cristae, which form invaginations, and the inner boundary membrane, which is located adjacent to the mitochondrial outer membrane.

Narrow apertures at the beginning of cristae of the mitochondrial inner membrane that link cristae to the inner boundary membrane.

Mutations or deletions in different genes that result in a stronger growth defect if combined in the same cell.

A mitochondrial DNA–protein assembly located in the matrix containing the packaging factor mitochondrial transcription factor A (TFAM).

ER–mitochondria encounter structure

(ERMES). A multisubunit protein complex that connects the endoplasmic reticulum (ER) and the mitochondrial outer membrane. ERMES is likely involved in lipid transfer between the organelles and is required for maintaining the morphology of mitochondria.


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