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Gene Review

MT-CO3  -  mitochondrially encoded cytochrome c...

Homo sapiens

Synonyms: CO3, COIII, COX3, COXIII, Cytochrome c oxidase polypeptide III, ...
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Disease relevance of MT-CO3


High impact information on MT-CO3

  • COX-3: just another COX or the solitary elusive target of paracetamol [6]?
  • Dicyclohexyl carbodiimide (DCCD) modifies a conserved glutamic acid residue in COIII and abolishes the proton translocation activity of the enzyme [7].
  • COIII is one of the major subunits in the mitochondrial and a bacterial cytochrome c oxidase, cytochrome aa3 [2].
  • The mutant phenotype can be complemented by introducing the COIII gene back to cells in a plasmid vector [2].
  • This suggests that the region of base pairing between individual guide RNAs and the COIII transcript is not strictly conserved in kinetoplastids, implying gradual evolution of the editing process [8].

Biological context of MT-CO3


Anatomical context of MT-CO3


Associations of MT-CO3 with chemical compounds

  • Two previously unreported amino acid replacements were detected in a third individual: amino acid 193 of cytochrome b was changed from alanine to threonine, and amino acid 88 of COIII was changed from threonine to alanine [17].
  • Pre-edited COII mRNA was similarly cleaved adjacent to its small editing domain, while pre-edited COIII RNA was cleaved at multiple sites in the region where uridine addition and deletion occurs in vivo [18].
  • COX-3, a variant of COX-1, has been found in canine brain and is inhibited by acetaminophen and dipyrone at physiological concentrations [19].
  • Estrogen-nucleic acid adducts: guanine is major site for interaction between 3,4-estrone quinone and COIII gene [20].
  • The observation that obstruction of in vitro replication of COIII template bound to 3,4-EQ suggests that estrogen quinone adducted lesions can arrest DNA polymerase [20].

Other interactions of MT-CO3

  • Loss of these two residues removes the termination codon for MTATP6 and sets MTCO3 immediately in frame [21].
  • In parallel, total RNA was extracted from samples of dissected heart and analyzed by Northern blot hybridization to determine the steady-state level of three RNA transcripts encoded by the COXII, COXIII, and COXIV genes [22].
  • The mRNA levels for the mtDNA-encoded 12 S rRNA, ND2, ATPase6+8, COIII, ND5+6, and Cytb genes were also increased, whereas the mtDNA number declined [23].
  • Three genes (COIII, NADH3 and NADH4) were not terminated by a stop codon [24].
  • Nucleotide substitutions with a potential for phenotypic effects were found in the 12S and 16S rRNA and in the ND1 and COIII genes [25].

Analytical, diagnostic and therapeutic context of MT-CO3

  • Northern Blot and quantitative real-time reverse transcription-PCR analysis further demonstrated that the primary ATP6--COX3 transcript is cleaved to the ATP6 and COX3 mRNAs 2-3-fold less efficiently [26].
  • Sequence analysis of muscle mtDNA resulted in the identification of a virtually homoplasmic frameshift mutation in the COIII gene, due to the insertion of an extra C at nucleotide position 9537 of mtDNA [27].
  • A PCR analysis of 21 cox3 clones, designed to measure the length of 5' and 3' ends separately, indicated that the greatest variability in length was found at the 3' end [12].
  • In this study, the invariant carboxylic acids E98 (the DCCD-binding glutamic acid) and D259 of COIII were changed by site-directed mutagenesis to study their role in proton pumping [7].
  • Northern hybridizations with potato and cauliflower (Brassica oleraceae) mtRNA and RT-PCR analyses using potato mtRNA indicated that cox3 and sdh4 are co-transcribed in both species, generating a complex transcription pattern, where several transcripts from 1.1 kb to 4.4 kb are found [28].


  1. Cytochrome c oxidase mutations in Leber hereditary optic neuropathy. Johns, D.R., Neufeld, M.J. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
  2. Deletion of the gene for subunit III leads to defective assembly of bacterial cytochrome oxidase. Haltia, T., Finel, M., Harms, N., Nakari, T., Raitio, M., Wikström, M., Saraste, M. EMBO J. (1989) [Pubmed]
  3. Effects of fatty acids on expression of genes encoding subunits of cytochrome c oxidase and cytochrome c oxidase activity in HT29 human colonic adenocarcinoma cells. Heerdt, B.G., Augenlicht, L.H. J. Biol. Chem. (1991) [Pubmed]
  4. A pathogenic 15-base pair deletion in mitochondrial DNA-encoded cytochrome c oxidase subunit III results in the absence of functional cytochrome c oxidase. Hoffbuhr, K.C., Davidson, E., Filiano, B.A., Davidson, M., Kennaway, N.G., King, M.P. J. Biol. Chem. (2000) [Pubmed]
  5. Expression of mitochondrial cytochrome c oxidase in human colonic cell differentiation, transformation, and risk for colonic cancer. Heerdt, B.G., Halsey, H.K., Lipkin, M., Augenlicht, L.H. Cancer Res. (1990) [Pubmed]
  6. COX-3: just another COX or the solitary elusive target of paracetamol? Schwab, J.M., Schluesener, H.J., Laufer, S. Lancet (2003) [Pubmed]
  7. Subunit III of cytochrome c oxidase is not involved in proton translocation: a site-directed mutagenesis study. Haltia, T., Saraste, M., Wikström, M. EMBO J. (1991) [Pubmed]
  8. The boundaries of partially edited transcripts are not conserved in kinetoplastids: implications for the guide RNA model of editing. Landweber, L.F., Fiks, A.G., Gilbert, W. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  9. Somatic mitochondrial DNA mutations in oral cancer of betel quid chewers. Tan, D.J., Chang, J., Chen, W.L., Agress, L.J., Yeh, K.T., Wang, B., Wong, L.J. Ann. N. Y. Acad. Sci. (2004) [Pubmed]
  10. Nucleotide sequence of the cox3 gene from Chondrus crispus: evidence that UGA encodes tryptophan and evolutionary implications. Boyen, C., Leblanc, C., Bonnard, G., Grienenberger, J.M., Kloareg, B. Nucleic Acids Res. (1994) [Pubmed]
  11. Novel heteroplasmic frameshift and missense somatic mitochondrial DNA mutations in oral cancer of betel quid chewers. Tan, D.J., Chang, J., Chen, W.L., Agress, L.J., Yeh, K.T., Wang, B., Wong, L.J. Genes Chromosomes Cancer (2003) [Pubmed]
  12. Polyadenylated transcripts containing random gene fragments are expressed in dinoflagellate mitochondria. Chaput, H., Wang, Y., Morse, D. Protist (2002) [Pubmed]
  13. Phylogeny of cephalopods inferred from mitochondrial DNA sequences. Bonnaud, L., Boucher-Rodoni, R., Monnerot, M. Mol. Phylogenet. Evol. (1997) [Pubmed]
  14. Two distinct, sequence-specific DNA-binding proteins interact independently with the major replication pause region of sea urchin mtDNA. Qureshi, S.A., Jacobs, H.T. Nucleic Acids Res. (1993) [Pubmed]
  15. Hypoxic depression of mitochondrial mRNA levels in HeLa cell. Kadowaki, T., Kitagawa, Y. Exp. Cell Res. (1991) [Pubmed]
  16. Identification of a new missense mutation in the mtDNA of hereditary hypertrophic, but not dilated cardiomyopathic hamsters. Minieri, M., Zingarelli, M., Shubeita, H., Vecchini, A., Binaglia, L., Carotenuto, F., Fantini, C., Fiaccavento, R., Masuelli, L., Coletti, A., Simonelli, L., Modesti, A., Di Nardo, P. Mol. Cell. Biochem. (2003) [Pubmed]
  17. Mitochondrial DNA mutations in patients with orthostatic hypotension. Schwartz, F., Baldwin, C.T., Baima, J., Gavras, H. Am. J. Med. Genet. (1999) [Pubmed]
  18. Specific cleavage of pre-edited mRNAs in trypanosome mitochondrial extracts. Harris, M., Decker, C., Sollner-Webb, B., Hajduk, S. Mol. Cell. Biol. (1992) [Pubmed]
  19. Variants of cyclooxygenase-1 and their roles in medicine. Simmons, D.L. Thromb. Res. (2003) [Pubmed]
  20. Estrogen-nucleic acid adducts: guanine is major site for interaction between 3,4-estrone quinone and COIII gene. Roy, D., Abul-Hajj, Y.J. Carcinogenesis (1997) [Pubmed]
  21. Investigation of a pathogenic mtDNA microdeletion reveals a translation-dependent deadenylation decay pathway in human mitochondria. Temperley, R.J., Seneca, S.H., Tonska, K., Bartnik, E., Bindoff, L.A., Lightowlers, R.N., Chrzanowska-Lightowlers, Z.M. Hum. Mol. Genet. (2003) [Pubmed]
  22. Structural and functional impairment of mitochondria in adriamycin-induced cardiomyopathy in mice: suppression of cytochrome c oxidase II gene expression. Papadopoulou, L.C., Theophilidis, G., Thomopoulos, G.N., Tsiftsoglou, A.S. Biochem. Pharmacol. (1999) [Pubmed]
  23. Neoplastic transformation is associated with coordinate induction of nuclear and cytoplasmic oxidative phosphorylation genes. Torroni, A., Stepien, G., Hodge, J.A., Wallace, D.C. J. Biol. Chem. (1990) [Pubmed]
  24. The complete mitochondrial DNA sequence of the horse, Equus caballus: extensive heteroplasmy of the control region. Xu, X., Arnason, U. Gene (1994) [Pubmed]
  25. A low rate of replacement substitutions in two major Ovis aries mitochondrial genomes. Hiendleder, S. Anim. Genet. (1998) [Pubmed]
  26. Diminished synthesis of subunit a (ATP6) and altered function of ATP synthase and cytochrome c oxidase due to the mtDNA 2 bp microdeletion of TA at positions 9205 and 9206. Jesina, P., Tesarová, M., Fornůsková, D., Vojtísková, A., Pecina, P., Kaplanová, V., Hansíková, H., Zeman, J., Houstek, J. Biochem. J. (2004) [Pubmed]
  27. A novel frameshift mutation of the mtDNA COIII gene leads to impaired assembly of cytochrome c oxidase in a patient affected by Leigh-like syndrome. Tiranti, V., Corona, P., Greco, M., Taanman, J.W., Carrara, F., Lamantea, E., Nijtmans, L., Uziel, G., Zeviani, M. Hum. Mol. Genet. (2000) [Pubmed]
  28. Transcription of succinate dehydrogenase subunit 4 (sdh4) gene in potato: detection of extensive RNA editing and co-transcription with cytochrome oxidase subunit III (cox3) gene. Siqueira, S.F., Dias, S.M., Hardouin, P., Pereira, F.R., Lejeune, B., de Souza, A.P. Curr. Genet. (2002) [Pubmed]
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