Open Access Articles- Top Results for Cytochrome c oxidase

Cytochrome c oxidase

Cytochrome c oxidase
EC number
CAS number 9001-16-5
IntEnz IntEnz view
ExPASy NiceZyme view
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

The enzyme cytochrome c oxidase, or Complex IV (EC, is a large transmembrane protein complex found in bacteria and the mitochondrion of eukaryotes.

It is the last enzyme in the respiratory electron transport chain of mitochondria or bacteria located in the mitochondrial or bacterial membrane. It receives an electron from each of four cytochrome c molecules, and transfers them to one oxygen molecule, converting molecular oxygen to two molecules of water. In the process, it binds four protons from the inner aqueous phase to make water, and in addition translocates four protons across the membrane, helping to establish a transmembrane difference of proton electrochemical potential that the ATP synthase then uses to synthesize ATP.[1][2]







Complex subunits

Conserved subunits of the cytochrome oxidase c complex:[8][9]

1 Cox1 COX1_HUMAN Cytochrome c oxidase subunit 1 Pfam PF00115
3 Cox3 COX3_HUMAN Cytochrome c oxidase subunit 3 Pfam PF00510
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
16 Cox7b COX7B_HUMAN Cytochrome c oxidase subunit 7B, mitochondrial Pfam PF05392
17 Cox7c COX7C_HUMAN Cytochrome c oxidase subunit 7C, mitochondrial Pfam PF02935
20 Cox8c COX8C_HUMAN Cytochrome c oxidase subunit 8C, mitochondrial Pfam PF02285
Assembly subunits[10][11][12]
1 Coa1 COA1_HUMAN Cytochrome c oxidase assembly factor 1 homolog Pfam PF08695
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
11 Cox17 COX17_HUMAN Cytochrome c oxidase copper chaperone Pfam PF05051
12 Cox18[13] 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


Summary reaction:




Cyanide, sulfide, azide, and carbon monoxide[14] all bind to cytochrome c oxidase, thus competitively inhibiting the protein from functioning, which results in chemical asphyxiation of cells. 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.[15]

Subcellular distribution

Cytochrome c oxidase has 3 subunits which are encoded by mitochondrial DNA. 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.[16] 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.[17][18] This raises the possibility about existence of yet unidentified specific mechanisms for protein translocation from mitochondria to other cellular destinations.[16][18][19]

Clinical significance





COX histochemistry is used for mapping regional brain metabolism in animals, since there is a direct relation between enzyme activity and neuronal activity.[22] Such brain mapping has been accomplished in spontaneous mutant mice with cerebellar disease such as reeler[23] and a transgenic model of Alzheimer's disease.[24] This technique has also been used to map learning activity in animal brain.[25]

Additional images

See also


  1. Yoshikawa, Shinya; Shimada, Atsuhiro; Shinzawa-Itoh, Kyoko (2015). "Chapter 4 Respiratory Conservation of Energy with Dioxygen: Cytochrome c Oxidase". In Peter M.H. Kroneck and Martha E. Sosa Torres. Sustaining Life on Planet Earth: Metalloenzymes Mastering Dioxygen and Other Chewy Gases. Metal Ions in Life Sciences 15. Springer. pp. 89–130. doi:10.1007/978-3-319-12415-5_4. 
  2. Yee, Gereon M.; Tolman, William B. (2015). "Chapter 5, Section 2.3 Iron-Porphyrin/Copper Complexes as Cytochrome c Oxidase Models". In Peter M.H. Kroneck and Martha E. Sosa Torres. Sustaining Life on Planet Earth: Metalloenzymes Mastering Dioxygen and Other Chewy Gases. Metal Ions in Life Sciences 15. Springer. pp. 153–157. doi:10.1007/978-3-319-12415-5_5. 
  3. Balsa E, Marco R, Perales-Clemente E, Szklarczyk R, Calvo E, Landázuri MO et al. (September 2012). "NDUFA4 is a subunit of complex IV of the mammalian electron transport chain". Cell Metab. 16 (3): 378–86. PMID 22902835. doi:10.1016/j.cmet.2012.07.015. 
  4. Tsukihara T, Aoyama H, Yamashita E, Tomizaki T, Yamaguchi H, Shinzawa-Itoh K et al. (August 1995). "Structures of metal sites of oxidized bovine heart cytochrome c oxidase at 2.8 A". Science 269 (5227): 1069–74. PMID 7652554. doi:10.1126/science.7652554. 
  6. Khalimonchuk O, Rödel G (December 2005). "Biogenesis of cytochrome c oxidase". Mitochondrion 5 (6): 363–88. PMID 16199211. doi:10.1016/j.mito.2005.08.002. 
  7. Fontanesi F, Soto IC, Horn D, Barrientos A (December 2006). "Assembly of mitochondrial cytochrome c-oxidase, a complicated and highly regulated cellular process". Am. J. Physiol., Cell Physiol. 291 (6): C1129–47. PMID 16760263. doi:10.1152/ajpcell.00233.2006. 
  8. Zhang Z, Huang L, Shulmeister VM, Chi YI, Kim KK, Hung LW et al. (1998). "Electron transfer by domain movement in cytochrome bc1.". Nature 392 (6677): 677–84. PMID 9565029. doi:10.1038/33612. 
  9. Kaila VR, Oksanen E, Goldman A, Bloch DA, Verkhovsky MI, Sundholm D et al. (2011). "A combined quantum chemical and crystallographic study on the oxidized binuclear center of cytochrome c oxidase.". Biochim Biophys Acta 1807 (7): 769–78. PMID 21211513. doi:10.1016/j.bbabio.2010.12.016. 
  10. Szklarczyk R, Wanschers BF, Cuypers TD, Esseling JJ, Riemersma M, van den Brand MA et al. (2012). "Iterative orthology prediction uncovers new mitochondrial proteins and identifies C12orf62 as the human ortholog of COX14, a protein involved in the assembly of cytochrome c oxidase.". Genome Biol 13 (2): R12. PMC 3334569. PMID 22356826. doi:10.1186/gb-2012-13-2-r12. 
  11. Mick DU, Dennerlein S, Wiese H, Reinhold R, Pacheu-Grau D, Lorenzi I et al. (2012). "MITRAC links mitochondrial protein translocation to respiratory-chain assembly and translational regulation.". Cell 151 (7): 1528–41. PMID 23260140. doi:10.1016/j.cell.2012.11.053. 
  12. Kozjak-Pavlovic V, Prell F, Thiede B, Götz M, Wosiek D, Ott C et al. (2014). "C1orf163/RESA1 is a novel mitochondrial intermembrane space protein connected to respiratory chain assembly.". J Mol Biol 426 (4): 908–20. PMID 24333015. doi:10.1016/j.jmb.2013.12.001. 
  13. Gaisne M, Bonnefoy N (2006). "The COX18 gene, involved in mitochondrial biogenesis, is functionally conserved and tightly regulated in humans and fission yeast.". FEMS Yeast Res 6 (6): 869–82. PMID 16911509. doi:10.1111/j.1567-1364.2006.00083.x. 
  14. Alonso JR, Cardellach F, López S, Casademont J, Miró O (September 2003). "Carbon monoxide specifically inhibits cytochrome c oxidase of human mitochondrial respiratory chain". Pharmacol. Toxicol. 93 (3): 142–6. PMID 12969439. doi:10.1034/j.1600-0773.2003.930306.x. 
  15. Arnold S, Kadenbach B (October 1997). "Cell respiration s controlled by ATP, an allosteric inhibitor of cytochrome-c oxidase.". Eur J Biochem 249: 350–254. PMID 9363790. doi:10.1111/j.1432-1033.1997.t01-1-00350.x. 
  16. 16.0 16.1 Sadacharan SK, Singh B, Bowes T, Gupta RS (2005). "Localization of mitochondrial DNA encoded cytochrome c oxidase subunits I and II in rat pancreatic zymogen granules and pituitary growth hormone granules". Histochem. Cell Biol. 124 (5): 409–21. PMID 16133117. doi:10.1007/s00418-005-0056-2. 
  17. Gupta RS, Ramachandra NB, Bowes T, Singh B (2008). "Unusual cellular disposition of the mitochondrial molecular chaperones Hsp60, Hsp70 and Hsp10". Novartis Found. Symp. 291: 59–68; discussion 69–73, 137–40. PMID 18575266. doi:10.1002/9780470754030.ch5. 
  18. 18.0 18.1 Soltys BJ, Gupta RS (2000). "Mitochondrial proteins at unexpected cellular locations: export of proteins from mitochondria from an evolutionary perspective". Int. Rev. Cytol. 194: 133–96. PMID 10494626. doi:10.1016/s0074-7696(08)62396-7. 
  19. Soltys BJ, Gupta RS (1999). "Mitochondrial-matrix proteins at unexpected locations: are they exported?". Trends Biochem. Sci. 24 (5): 174–7. PMID 10322429. doi:10.1016/s0968-0004(99)01390-0. 
  21. Zee JM, Glerum DM (December 2006). "Defects in cytochrome oxidase assembly in humans: lessons from yeast". Biochem. Cell Biol. 84 (6): 859–69. PMID 17215873. doi:10.1139/o06-201. 
  22. Wong-Riley MT (1989). "Cytochrome oxidase: an endogenous metabolic marker for neuronal activity.". Trends Neurosci. 12 (3): 94–111. PMID 2469224. doi:10.1016/0166-2236(89)90165-3. 
  23. Strazielle C, Hayzoun K, Derer M, Mariani J, Lalonde R (April 2006). "Regional brain variations of cytochrome oxidase activity in Relnrl-orl mutant mice.". J. Neurosci. Res. 83 (5): 821–31. PMID 16511878. doi:10.1002/jnr.20772. 
  24. Strazielle C, Sturchler-Pierrat C, Staufenbiel M, Lalonde R (2003). "Regional brain cytochrome oxidase activity in beta-amyloid precursor protein transgenic mice with the Swedish mutation.". Neuroscience 118 (4): 1151–63. PMID 12732258. doi:10.1016/S0306-4522(03)00037-X. 
  25. Conejo NM, González-Pardo H, Gonzalez-Lima F, Arias JL (2010). "Spatial learning of the water maze: progression of brain circuits mapped with cytochrome oxidase histochemistry.". Neurobiol. Learn. Mem. 93 (3): 362–71. PMID 19969098. doi:10.1016/j.nlm.2009.12.002. 

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