Cytochrome c oxidase

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Cytochrome c oxidase
Cytochrome C Oxidase 1OCC in Membrane 2.png
The crystal structure of bovine cytochrome c oxidase in a phospholipid bilayer. The intermembrane space lies to top of the image. Adapted from PDB: 1OCC ​ (It is a homodimer in this structure)
Identifiers
EC no. 1.9.3.1
CAS no. 9001-16-5
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MetaCyc metabolic pathway
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NCBI proteins
Cytochrome c oxidase
Cmplx4.PNG
Subunit I and II of Complex IV excluding all other subunits, PDB: 2EIK ​
Identifiers
SymbolCytochrome c oxidase
OPM superfamily 4
OPM protein 2dyr
Membranome 257

The enzyme cytochrome c oxidase or Complex IV, (was EC 1.9.3.1, now reclassified as a translocase EC 7.1.1.9) is a large transmembrane protein complex found in bacteria, archaea, and the mitochondria of eukaryotes. [1]

Contents

It is the last enzyme in the respiratory electron transport chain of cells located in the membrane. It receives an electron from each of four cytochrome c molecules and transfers them to one oxygen molecule and four protons, producing two molecules of water. In addition to binding the four protons from the inner aqueous phase, it transports another four protons across the membrane, increasing the transmembrane difference of proton electrochemical potential, which the ATP synthase then uses to synthesize ATP.

Structure

The complex

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 Fe3+. 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 and four protons 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

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

Assembly

COX assembly in yeast are 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. Over 30 different nuclear-encoded chaperone proteins are required for COX assembly. [12]

Cofactors, including hemes, 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. [13] 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. Dimers are connected by a cardiolipin molecule, [11] [14] [15] 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. [15] 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. [16] [17] 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. [18]

Biochemistry

The overall reaction is

4 Fe2+ – cytochrome c + 4 H+ + O2 → 4 Fe3+ – cytochrome c + 2 H2O ΔfGo' = - 218 kJ/mol

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 Fe2+ 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 Fe2+-cytochrome a3, which is converted to the ferryl oxo form (Fe4+=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 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 CuB2+ 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 Fe4+=O to Fe3+, 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. Overall, four reduced cytochrome c's are oxidized while O2 and four protons are reduced to two water molecules. [4] : 841–5 

Inhibition

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 Fe2+ at the cytochrome a3 heme group and a reduced CuB+ binuclear center, is considered the inactive or resting state of the enzyme. [19]

Cyanide, azide, and carbon monoxide [20] 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 decrease 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. [21]

Cyanide is a non-competitive inhibitor for COX, [22] [23] 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. [24]

Nitric oxide can reversibly [25] 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. [19] 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. [25] NO inhibition of Complex IV has a larger effect at lower oxygen concentrations, increasing its utility as a vasodilator in tissues of need. [25]

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. [21]

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. [26]

Extramitochondrial and subcellular localizations

Location of the 3 cytochrome c oxidase subunit genes in the human mitochondrial genome: COXI, COXII, and COXIII (orange boxes). Map of the human mitochondrial genome.svg
Location of the 3 cytochrome c oxidase subunit genes in the human mitochondrial genome: COXI , COXII , and COXIII (orange boxes).

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. [27] 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. [28] [29] This raises the possibility about existence of yet unidentified specific mechanisms for protein translocation from mitochondria to other cellular destinations. [27] [29] [30]

Genetic defects and disorders

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. [31]

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. [32]

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.

Histochemistry

The increased reliance of neurons on oxidative phosphorylation for energy [33] 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. [34] 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. [35] Such brain mapping has been accomplished in spontaneous mutant mice with cerebellar disease such as reeler [36] and a transgenic model of Alzheimer's disease. [37] This technique has also been used to map learning activity in the animal brain. [38]

Additional images

See also

Related Research Articles

<span class="mw-page-title-main">Oxidative phosphorylation</span> Metabolic pathway

Oxidative phosphorylation or electron transport-linked phosphorylation or terminal oxidation is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing chemical energy in order to produce adenosine triphosphate (ATP). In eukaryotes, this takes place inside mitochondria. Almost all aerobic organisms carry out oxidative phosphorylation. This pathway is so pervasive because it releases more energy than alternative fermentation processes such as anaerobic glycolysis.

An electron transport chain (ETC) is a series of protein complexes and other molecules that transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples this electron transfer with the transfer of protons (H+ ions) across a membrane. Many of the enzymes in the electron transport chain are embedded within the membrane.

<span class="mw-page-title-main">Coenzyme Q – cytochrome c reductase</span> Class of enzymes

The coenzyme Q : cytochrome c – oxidoreductase, sometimes called the cytochrome bc1 complex, and at other times complex III, is the third complex in the electron transport chain, playing a critical role in biochemical generation of ATP. Complex III is a multisubunit transmembrane protein encoded by both the mitochondrial and the nuclear genomes. Complex III is present in the mitochondria of all animals and all aerobic eukaryotes and the inner membranes of most eubacteria. Mutations in Complex III cause exercise intolerance as well as multisystem disorders. The bc1 complex contains 11 subunits, 3 respiratory subunits, 2 core proteins and 6 low-molecular weight proteins.

<span class="mw-page-title-main">Alternative oxidase</span>

The alternative oxidase (AOX) is an enzyme that forms part of the electron transport chain in mitochondria of different organisms. Proteins homologous to the mitochondrial oxidase and the related plastid terminal oxidase have also been identified in bacterial genomes.

<span class="mw-page-title-main">Nitrous-oxide reductase</span> Class of enzymes

In enzymology, a nitrous oxide reductase also known as nitrogen:acceptor oxidoreductase (N2O-forming) is an enzyme that catalyzes the final step in bacterial denitrification, the reduction of nitrous oxide to dinitrogen.

<span class="mw-page-title-main">Cytochrome c oxidase subunit I</span> Enzyme of the respiratory chain encoded by the mitochondrial genome

Cytochrome c oxidase I (COX1) also known as mitochondrially encoded cytochrome c oxidase I (MT-CO1) is a protein that is encoded by the MT-CO1 gene in eukaryotes. The gene is also called COX1, CO1, or COI. Cytochrome c oxidase I is the main subunit of the cytochrome c oxidase complex. In humans, mutations in MT-CO1 have been associated with Leber's hereditary optic neuropathy (LHON), acquired idiopathic sideroblastic anemia, Complex IV deficiency, colorectal cancer, sensorineural deafness, and recurrent myoglobinuria.

<span class="mw-page-title-main">Cytochrome c oxidase subunit 2</span> Enzyme of the respiratory chain encoded by the mitochondrial genome

Cytochrome c oxidase II is a protein in eukaryotes that is encoded by the MT-CO2 gene. Cytochrome c oxidase subunit II, abbreviated COXII, COX2, COII, or MT-CO2, is the second subunit of cytochrome c oxidase. It is also one of the three mitochondrial DNA (mtDNA) encoded subunits of respiratory complex IV.

<span class="mw-page-title-main">SCO2</span> Protein-coding gene in the species Homo sapiens

SCO2 cytochrome c oxidase assembly is a protein that in humans is encoded by the SCO2 gene. The encoded protein is one of the cytochrome c oxidase (COX)(Complex IV) assembly factors. Human COX is a multimeric protein complex that requires several assembly factors. Cytochrome c oxidase (COX) catalyzes the transfer of electrons from cytochrome c to molecular oxygen, which helps to maintain the proton gradient across the inner mitochondrial membrane that is necessary for aerobic ATP production. The encoded protein is a metallochaperone that is involved in the biogenesis of cytochrome c oxidase subunit II. Mutations in this gene are associated with fatal infantile encephalocardiomyopathy and myopia 6.

<span class="mw-page-title-main">COX4I1</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase subunit 4 isoform 1, mitochondrial (COX4I1) is an enzyme that in humans is encoded by the COX4I1 gene. COX4I1 is a nuclear-encoded isoform of cytochrome c oxidase (COX) subunit 4. Cytochrome c oxidase is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to a proton electrochemical gradient across the inner mitochondrial membrane, acting as the terminal enzyme of the mitochondrial respiratory chain. Antibodies against COX4 can be used to identify the inner membrane of mitochondria in immunofluorescence studies. Mutations in COX4I1 have been associated with COX deficiency and Fanconi anemia.

<span class="mw-page-title-main">COX4I2</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase subunit 4 isoform 2, mitochondrial is an enzyme that in humans is encoded by the COX4I2 gene. COX4I2 is a nuclear-encoded isoform of cytochrome c oxidase (COX) subunit 4. Cytochrome c oxidase is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to a proton electrochemical gradient across the inner mitochondrial membrane, acting as the terminal enzyme of the mitochondrial respiratory chain. Mutations in COX4I2 have been associated with exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis (EPIDACH).

<span class="mw-page-title-main">COX6B1</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase subunit 6B1 is an enzyme that in humans is encoded by the COX6B1 gene. Cytochrome c oxidase 6B1 is a subunit of the cytochrome c oxidase complex, also known as Complex IV, the last enzyme in the mitochondrial electron transport chain. Mutations of the COX6B1 gene are associated with severe infantile encephalomyopathy and mitochondrial complex IV deficiency (MT-C4D).

<span class="mw-page-title-main">COX5B</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase subunit 5B, mitochondrial is an enzyme in humans that is a subunit of the cytochrome c oxidase complex, also known as Complex IV, the last enzyme in the mitochondrial electron transport chain. In humans, cytochrome c oxidase subunit 5B is encoded by the COX5B gene.

<span class="mw-page-title-main">COX6A1</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase subunit 6A1, mitochondrial is a protein that in humans is encoded by the COX6A1 gene. Cytochrome c oxidase 6A1 is a subunit of the cytochrome c oxidase complex, also known as Complex IV, the last enzyme in the mitochondrial electron transport chain. A mutation of the COX6A1 gene is associated with a recessive axonal or mixed form of Charcot-Marie-Tooth disease.

<span class="mw-page-title-main">COX7B</span> Protein-coding gene in humans

Cytochrome c oxidase subunit 7B, mitochondrial (COX7B) is an enzyme that in humans is encoded by the COX7B gene. COX7B is a nuclear-encoded subunit of cytochrome c oxidase (COX). Cytochrome c oxidase is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to a proton electrochemical gradient across the inner mitochondrial membrane, acting as the terminal enzyme of the mitochondrial respiratory chain. Work with Oryzias latices has linked disruptions in COX7B with microphthalmia with linear skin lesions (MLS), microcephaly, and mitochondrial disease. Clinically, mutations in COX7B have been associated with linear skin defects with multiple congenital anomalies.

<span class="mw-page-title-main">COX7A2L</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase subunit 7A-related protein, mitochondrial is an enzyme that in humans is encoded by the COX7A2L gene.

<span class="mw-page-title-main">COX6C</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase subunit 6C is an enzyme that in humans is encoded by the COX6C gene.

<span class="mw-page-title-main">COX5A</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase subunit 5a is a protein that in humans is encoded by the COX5A gene. Cytochrome c oxidase 5A is a subunit of the cytochrome c oxidase complex, also known as Complex IV, the last enzyme in the mitochondrial electron transport chain.

<span class="mw-page-title-main">COX6A2</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase subunit VIa polypeptide 2 is a protein that in humans is encoded by the COX6A2 gene. Cytochrome c oxidase 6A2 is a subunit of the cytochrome c oxidase complex, also known as Complex IV, the last enzyme in the mitochondrial electron transport chain.

<span class="mw-page-title-main">COX6B2</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase subunit VIb polypeptide 2 is a protein that in humans is encoded by the COX6B2 gene. Cytochrome c oxidase 6B2 is a subunit of the cytochrome c oxidase complex, also known as Complex IV, the last enzyme in the mitochondrial electron transport chain.

<span class="mw-page-title-main">COX8A</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase subunit 8A (COX8A) is a protein that in humans is encoded by the COX8A gene. Cytochrome c oxidase 8A is a subunit of the cytochrome c oxidase complex, also known as Complex IV. Mutations in the COX8A gene have been associated with complex IV deficiency with Leigh syndrome and epilepsy.

References

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