Protoheme IX farnesyltransferase, mitochondrial is an enzyme that in humans is encoded by the COX10gene.[1][2]
Cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene encodes heme A:farnesyltransferase, which is not a structural subunit but required for the expression of functional COX and functions in the maturation of the heme A prosthetic group of COX. This protein is predicted to contain 7-9 transmembrane domains localized in the mitochondrial inner membrane. A gene mutation, which results in the substitution of a lysine for an asparagine (N204K), is identified to be responsible for cytochrome c oxidase deficiency. In addition, this gene is disrupted in patients with CMT1A (Charcot-Marie-Tooth type 1A) duplication and with HNPP (hereditary neuropathy with liability to pressure palsies) deletion.[2]
References
↑Murakami T, Reiter LT, Lupski JR (Jul 1997). "Genomic structure and expression of the human heme A:farnesyltransferase (COX10) gene". Genomics. 42 (1): 161–4. doi:10.1006/geno.1997.4711. PMID9177788.
Reiter LT, Murakami T, Koeuth T, et al. (1998). "The human COX10 gene is disrupted during homologous recombination between the 24 kb proximal and distal CMT1A-REPs". Hum. Mol. Genet. 6 (9): 1595–603. doi:10.1093/hmg/6.9.1595. PMID9285799.
Kennerson ML, Nassif NT, Dawkins JL, et al. (1998). "The Charcot-Marie-Tooth binary repeat contains a gene transcribed from the opposite strand of a partially duplicated region of the COX10 gene". Genomics. 46 (1): 61–9. doi:10.1006/geno.1997.5012. PMID9403059.
Kennerson ML, Nassif NT, Nicholson GA (1998). "Genomic structure and physical mapping of C17orf1: a gene associated with the proximal element of the CMT1A-REP binary repeat". Genomics. 53 (1): 110–2. doi:10.1006/geno.1998.5453. PMID9787083.
Valnot I, von Kleist-Retzow JC, Barrientos A, et al. (2000). "A mutation in the human heme A:farnesyltransferase gene (COX10 ) causes cytochrome c oxidase deficiency". Hum. Mol. Genet. 9 (8): 1245–9. doi:10.1093/hmg/9.8.1245. PMID10767350.
Bosetti F, Brizzi F, Barogi S, et al. (2002). "Cytochrome c oxidase and mitochondrial F1F0-ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer's disease". Neurobiol. Aging. 23 (3): 371–6. doi:10.1016/S0197-4580(01)00314-1. PMID11959398.
Antonicka H, Leary SC, Guercin GH, et al. (2004). "Mutations in COX10 result in a defect in mitochondrial heme A biosynthesis and account for multiple, early-onset clinical phenotypes associated with isolated COX deficiency". Hum. Mol. Genet. 12 (20): 2693–702. doi:10.1093/hmg/ddg284. PMID12928484.
Williams SL, Valnot I, Rustin P, Taanman JW (2004). "Cytochrome c oxidase subassemblies in fibroblast cultures from patients carrying mutations in COX10, SCO1, or SURF1". J. Biol. Chem. 279 (9): 7462–9. doi:10.1074/jbc.M309232200. PMID14607829.
Coenen MJ, van den Heuvel LP, Ugalde C, et al. (2004). "Cytochrome c oxidase biogenesis in a patient with a mutation in COX10 gene". Ann. Neurol. 56 (4): 560–4. doi:10.1002/ana.20229. PMID15455402.
Veluthakal R, Kaur H, Goalstone M, Kowluru A (2007). "Dominant-negative alpha-subunit of farnesyl- and geranyltransferase inhibits glucose-stimulated, but not KCl-stimulated, insulin secretion in INS 832/13 cells". Diabetes. 56 (1): 204–10. doi:10.2337/db06-0668. PMID17192483.
