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Gene Review

MT-CO1  -  mitochondrially encoded cytochrome c...

Homo sapiens

Synonyms: COI, COX1, COXI, Cytochrome c oxidase polypeptide I, Cytochrome c oxidase subunit 1, ...
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Disease relevance of MT-CO1


Psychiatry related information on MT-CO1

  • These data with exploratory behavior and laparotomy agree with studies with reflexive withdrawal responses after incisional surgery and indicate that COX-1 inhibition reduces pain responses after surgery [6].
  • Exploratory locomotor activity was measured on the first postoperative day after intrathecal injection of dimethyl sulfoxide (vehicle) or COX-1 (SC-560) or COX-2 (NS-398) inhibitors [6].
  • Nearly three fourths of journal editors surveyed usually publish author disclosure statements suggesting that low rates of personal financial disclosures are either a result of low rates of author financial interest in the subject matter of their publications or poor compliance by authors to the journals' COI policies [7].
  • Costs of alcohol and drug abuse in the United States, 1992. Alcohol/Drugs COI Study Team [8].

High impact information on MT-CO1

  • Mitochondrial genome rearrangement leads to extension and relocation of the cytochrome c oxidase subunit I gene in sorghum [9].
  • A variant COI observed in 9E cytoplasm (Mr approximately 42,000) is encoded by a 631 codon structural gene that diverges completely from the Milo COXI gene both 100 bp 5' to the presumed initiator methionine and within the 3' coding sequence [9].
  • Nuclear respiratory factor 2 (NRF-2) is a nuclear transcription factor that activates the proximal promoter of the rat cytochrome c oxidase subunit IV (RCO4) gene through tandem sequence elements [10].
  • Sarcoma-180 cells implanted in wild-type (WT) mice formed a tumor with extensive angiogenesis, which was greatly suppressed by specific inhibitors for cyclooxygenase (COX)-2 but not for COX-1 [11].
  • For example, recent work suggests that the long-sought-after target of the analgesic acetaminophen is a neural-specific, alternatively spliced isoform of cyclooxygenase 1 (COX-1) [12].

Chemical compound and disease context of MT-CO1

  • OBJECTIVE: To classify patients with a history of aspirin-induced urticaria as cross-reactors or single-drug reactors by oral challenges with another strong COX-1 inhibitor, namely, ketoprofen [13].
  • OBJECTIVE: To investigate the activities of the 2 isoforms of prostaglandin synthetic enzyme cyclo-oxygenase (COX), COX-1 and COX-2, in the placental tissue of women with pre-eclampsia and healthy pregnant women [14].
  • CONCLUSION: The increases of COX-1, COX-2, mPGES-1 and EP1-2 in epithelial ovarian cancer, supports the hypothesis that PGE2-synthesis and signalling are of importance for malignant transformation and progression [15].
  • The correlation analysis showed significant negative correlations between MDA and COX-1 (r=-0.44, P<0.001) and MDA and COX-2 (r=-0.45, P<0.001) in the placental tissue of women with pre-eclampsia [14].
  • In this report, we evaluated the growth-inhibitory effects of sulindac sulfide, a COX-1 and COX-2 inhibitor; exisulind (sulindac sulfone), a novel proapoptotic agent that does not inhibit COX enzymes; and nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor on human lung cancer cell lines [16].

Biological context of MT-CO1


Anatomical context of MT-CO1


Associations of MT-CO1 with chemical compounds

  • Our objective herein was to further elucidate the relationships among LH stimulation, Leydig cell COX2 and COX1 expression, aging, and testosterone production [26].
  • COX1 expression did not respond to LH or dibutyryl cAMP [26].
  • Sodium salicylate exerted similar effects on SR-BI expression, whereas no effects were observed using known COX1/2 inhibitors ibuprofen and naproxen, respectively [27].
  • In WT mice, the dilation to ACh declined at 12 mo but was insensitive to COX-1/2 inhibition alone or with NAC [28].
  • Treatment by low concentrations of celecoxib did not alter the levels of COX-1, beta-catenin, P(27), Bcl-2, and Bcl-x proteins [29].

Other interactions of MT-CO1

  • RESULTS: Morphologically, we found abnormal mitochondrial proliferation with several cytochrome-c oxidase (COX)-negative fibers in muscle biopsy specimens; the analysis of serial sections showed a decreased immunoreactivity for the mtDNA-encoded subunits COXII and, partially, COXI [30].
  • Mitochondrial DNA regions in the cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase subunit 1 (nad1) genes were amplified by PCR from total genomic DNA samples (n > 720) from Ascaris individuals from humans and pigs, and subjected to mutation scanning and subsequent selective sequencing [31].
  • Here, we show that the COX-1 inhibitors, selective or not, and sulindac sulfone, a non-COX inhibitor, increased 15-PGDH activity and reduced PGE(2) levels [22].
  • Structure of the human gene (COX6A2) for the heart/muscle isoform of cytochrome c oxidase subunit VIa and its chromosomal location in humans, mice, and cattle [32].
  • Similarly, complex IV mutation COI/7444 was screened in Finnish LHON families, and it was found in one family carrying the ND1/3460 mutation [33].

Analytical, diagnostic and therapeutic context of MT-CO1

  • The level of mRNA for cytochrome C oxidase subunit I (COX-I), which is encoded by mitochondrial DNA (mtDNA), progressively deceased in the hippocampal CA1 neurons of gerbils from 3 hours of the reperfusion after 3.5 min of transient forebrain ischemia, and completely disappeared at 7 days [34].
  • A clone encoding cytochrome c oxidase subunit 1 was found and confirmed to have been upregulated by northern blotting [35].
  • COII data, worker morphometry and male genitalia morphology corroborated the COI results for seven lineages; the remaining six were disregarded because of small sample size [36].
  • The expression of cyclooxygenase (COX)-2 and IL-1beta mRNA (messenger ribonucleic acid) was enhanced by mechanical tension as determined by use of reverse transcription-polymerase chain reaction (RT-PCR), whereas COX-1 and IL-1beta-converting enzyme mRNA remained unchanged [37].
  • The expression and cell-specific localization of COX-1, COX-2, microsomal prostaglandin E synthase-1 (mPGES-1) and two of the receptors for PGE2, EP1 and EP2, were examined by immunoblotting (IB) and immunohistochemistry (IHC) [15].


  1. A mitochondrial DNA variant, identified in Leber hereditary optic neuropathy patients, which extends the amino acid sequence of cytochrome c oxidase subunit I. Brown, M.D., Yang, C.C., Trounce, I., Torroni, A., Lott, M.T., Wallace, D.C. Am. J. Hum. Genet. (1992) [Pubmed]
  2. In vivo regulation of oxidative phosphorylation in cells harboring a stop-codon mutation in mitochondrial DNA-encoded cytochrome c oxidase subunit I. D'Aurelio, M., Pallotti, F., Barrientos, A., Gajewski, C.D., Kwong, J.Q., Bruno, C., Beal, M.F., Manfredi, G. J. Biol. Chem. (2001) [Pubmed]
  3. Inhibition of cytochrome c oxidase subunit 4 precursor processing by the hypoxia mimic cobalt chloride. Hervouet, E., Pecina, P., Demont, J., Vojtísková, A., Simonnet, H., Houstek, J., Godinot, C. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  4. Mutations in mtDNA-encoded cytochrome c oxidase subunit genes causing isolated myopathy or severe encephalomyopathy. Horváth, R., Schoser, B.G., Müller-Höcker, J., Völpel, M., Jaksch, M., Lochmüller, H. Neuromuscul. Disord. (2005) [Pubmed]
  5. All-trans retinoic acid induces COX-2 and prostaglandin E2 synthesis in SH-SY5Y human neuroblastoma cells: involvement of retinoic acid receptors and extracellular-regulated kinase 1/2. Alique, M., Herrero, J.F., Lucio-Cazana, F.J. Journal of neuroinflammation (2007) [Pubmed]
  6. Intrathecal administration of a cylcooxygenase-1, but not a cyclooxygenase-2 inhibitor, reverses the effects of laparotomy on exploratory activity in rats. Martin, T.J., Buechler, N.L., Eisenach, J.C. Anesth. Analg. (2006) [Pubmed]
  7. Conflict of interest policies in science and medical journals: editorial practices and author disclosures. Krimsky, S., Rothenberg, L.S. Science and engineering ethics. (2001) [Pubmed]
  8. Costs of alcohol and drug abuse in the United States, 1992. Alcohol/Drugs COI Study Team. Holland, P., Mushinski, M. Statistical bulletin (Metropolitan Life Insurance Company : 1984) (1999) [Pubmed]
  9. Mitochondrial genome rearrangement leads to extension and relocation of the cytochrome c oxidase subunit I gene in sorghum. Bailey-Serres, J., Hanson, D.K., Fox, T.D., Leaver, C.J. Cell (1986) [Pubmed]
  10. Identity of GABP with NRF-2, a multisubunit activator of cytochrome oxidase expression, reveals a cellular role for an ETS domain activator of viral promoters. Virbasius, J.V., Virbasius, C.A., Scarpulla, R.C. Genes Dev. (1993) [Pubmed]
  11. Host prostaglandin E(2)-EP3 signaling regulates tumor-associated angiogenesis and tumor growth. Amano, H., Hayashi, I., Endo, H., Kitasato, H., Yamashina, S., Maruyama, T., Kobayashi, M., Satoh, K., Narita, M., Sugimoto, Y., Murata, T., Yoshimura, H., Narumiya, S., Majima, M. J. Exp. Med. (2003) [Pubmed]
  12. Alternative splicing in disease and therapy. Garcia-Blanco, M.A., Baraniak, A.P., Lasda, E.L. Nat. Biotechnol. (2004) [Pubmed]
  13. Use of ketoprofen oral challenges to detect cross-reactors among patients with a history of aspirin-induced urticaria. Asero, R. Ann. Allergy Asthma Immunol. (2006) [Pubmed]
  14. Placental tissue cyclo-oxygenase 1 and 2 in pre-eclamptic and normal pregnancy. B??rek??i, B., Aksoy, H., Toker, A., Ozkan, A. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. (2006) [Pubmed]
  15. Ovarian epithelial cancer: a role for PGE2-synthesis and signalling in malignant transformation and progression. Rask, K., Zhu, Y., Wang, W., Hedin, L., Sundfeldt, K. Mol. Cancer (2006) [Pubmed]
  16. Synergistic effects of new chemopreventive agents and conventional cytotoxic agents against human lung cancer cell lines. Soriano, A.F., Helfrich, B., Chan, D.C., Heasley, L.E., Bunn, P.A., Chou, T.C. Cancer Res. (1999) [Pubmed]
  17. Activation of mitochondrial promoter P(H)-binding protein in a radio-resistant Chinese hamster cell strain associated with Bcl-2. Roychoudhury, P., Ghosh, U., Bhattacharyya, N.P., Chaudhuri, K. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  18. Impact of alkyl esters of caffeic and ferulic acids on tumor cell proliferation, cyclooxygenase enzyme, and lipid peroxidation. Jayaprakasam, B., Vanisree, M., Zhang, Y., Dewitt, D.L., Nair, M.G. J. Agric. Food Chem. (2006) [Pubmed]
  19. Rapid evolution of the human gene for cytochrome c oxidase subunit IV. Lomax, M.I., Hewett-Emmett, D., Yang, T.L., Grossman, L.I. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  20. Aspirin induces platelet receptor shedding via ADAM17 (TACE). Aktas, B., Pozgajova, M., Bergmeier, W., Sunnarborg, S., Offermanns, S., Lee, D., Wagner, D.D., Nieswandt, B. J. Biol. Chem. (2005) [Pubmed]
  21. Supernatant of bacterial fermented soybean induces apoptosis of human hepatocellular carcinoma Hep 3B cells via activation of caspase 8 and mitochondria. Su, C.L., Wu, C.J., Chen, F.N., Wang, B.J., Sheu, S.R., Won, S.J. Food Chem. Toxicol. (2007) [Pubmed]
  22. 15-Hydroxyprostaglandin-dehydrogenase is involved in anti-proliferative effect of non-steroidal anti-inflammatory drugs COX-1 inhibitors on a human medullary thyroid carcinoma cell line. Quidville, V., Segond, N., Lausson, S., Frenkian, M., Cohen, R., Jullienne, A. Prostaglandins Other Lipid Mediat. (2006) [Pubmed]
  23. Cytochrome c oxidase subunit I microdeletion in a patient with motor neuron disease. Comi, G.P., Bordoni, A., Salani, S., Franceschina, L., Sciacco, M., Prelle, A., Fortunato, F., Zeviani, M., Napoli, L., Bresolin, N., Moggio, M., Ausenda, C.D., Taanman, J.W., Scarlato, G. Ann. Neurol. (1998) [Pubmed]
  24. Development and age-associated differences in electron transport potential and consequences for oxidant generation. Allen, R.G., Keogh, B.P., Tresini, M., Gerhard, G.S., Volker, C., Pignolo, R.J., Horton, J., Cristofalo, V.J. J. Biol. Chem. (1997) [Pubmed]
  25. 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]
  26. Cyclooxygenases in rat Leydig cells: effects of luteinizing hormone and aging. Chen, H., Luo, L., Liu, J., Zirkin, B.R. Endocrinology (2007) [Pubmed]
  27. Aspirin regulates expression and function of scavenger receptor-BI in macrophages: studies in primary human macrophages and in mice. Tancevski, I., Wehinger, A., Schgoer, W., Eller, P., Cuzzocrea, S., Foeger, B., Patsch, J.R., Ritsch, A. FASEB J. (2006) [Pubmed]
  28. Aging associated with mild dyslipidemia reveals that COX-2 preserves dilation despite endothelial dysfunction. Gendron, M.E., Thorin-Trescases, N., Villeneuve, L., Thorin, E. Am. J. Physiol. Heart Circ. Physiol. (2007) [Pubmed]
  29. Down-Regulation of PGE(2) by Physiologic Levels of Celecoxib is not Sufficient to Induce Apoptosis or Inhibit Cell Proliferation in Human Colon Carcinoma Cell Lines. Lev-Ari, S., Kazanov, D., Liberman, E., Ben-Yosef, R., Arber, N. Dig. Dis. Sci. (2007) [Pubmed]
  30. Revelation of a new mitochondrial DNA mutation (G12147A) in a MELAS/MERFF phenotype. Melone, M.A., Tessa, A., Petrini, S., Lus, G., Sampaolo, S., di Fede, G., Santorelli, F.M., Cotrufo, R. Arch. Neurol. (2004) [Pubmed]
  31. Mutation scanning-coupled analysis of haplotypic variability in mitochondrial DNA regions reveals low gene flow between human and porcine Ascaris in endemic regions of China. Peng, W., Yuan, K., Hu, M., Zhou, X., Gasser, R.B. Electrophoresis (2005) [Pubmed]
  32. Structure of the human gene (COX6A2) for the heart/muscle isoform of cytochrome c oxidase subunit VIa and its chromosomal location in humans, mice, and cattle. Bachman, N.J., Riggs, P.K., Siddiqui, N., Makris, G.J., Womack, J.E., Lomax, M.I. Genomics (1997) [Pubmed]
  33. The spectrum of mitochondrial DNA mutations in families with Leber hereditary optic neuroretinopathy. Huoponen, K., Lamminen, T., Juvonen, V., Aula, P., Nikoskelainen, E., Savontaus, M.L. Hum. Genet. (1993) [Pubmed]
  34. Isolation of an ischemia-induced gene and early disturbance of mitochondrial DNA expression after transient forebrain ischemia. Abe, K., Kawagoe, J., Itoyama, Y., Kogure, K. Advances in neurology. (1996) [Pubmed]
  35. Differential expression of mitochondria-encoded genes in a hibernating mammal. Hittel, D.S., Storey, K.B. J. Exp. Biol. (2002) [Pubmed]
  36. A multidisciplinary approach reveals cryptic diversity in Western Palearctic Tetramorium ants (Hymenoptera: Formicidae). Schlick-Steiner, B.C., Steiner, F.M., Moder, K., Seifert, B., Sanetra, M., Dyreson, E., Stauffer, C., Christian, E. Mol. Phylogenet. Evol. (2006) [Pubmed]
  37. Stimulation of prostaglandin E2 and interleukin-1beta production from old rat periodontal ligament cells subjected to mechanical stress. Shimizu, N., Yamaguchi, M., Uesu, K., Goseki, T., Abiko, Y. J. Gerontol. A Biol. Sci. Med. Sci. (2000) [Pubmed]
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