A mutation in the human heme A:farnesyltransferase gene (COX10 ) causes cytochrome c oxidase deficiency - PubMed

Affiliations

• PMID: 10767350
• DOI: 10.1093/hmg/9.8.1245

Case Reports

A mutation in the human heme A:farnesyltransferase gene (COX10 ) causes cytochrome c oxidase deficiency

I Valnot et al. Hum Mol Genet. 2000.

Abstract

Cytochrome c oxidase (COX) defects are found in a clinically and genetically heterogeneous group of mitochondrial disorders. To date, mutations in only two nuclear genes causing COX deficiency have been described. We report here a genetic linkage study of a consanguineous family with an isolated COX defect and subsequent identification of a mutation in a third nuclear gene causing a deficiency of the enzyme. A genome-wide search for homozygosity allowed us to map the disease gene to chromosome 17p13.1-q11.1 (Z (max)= 2.46; theta = 0.00 at the locus D17S799). This region encompasses two genes, SCO1 and COX10, encoding proteins involved in COX assembly. Mutation analysis followed by a complementation study in yeast permitted us to ascribe the COX deficiency to a homozygous missense mutation in the COX10 gene. This gene encodes heme A:farnesyltransferase, which catalyzes the first step in the conversion of protoheme to the heme A prosthetic groups of the enzyme. All three nuclear genes now linked to isolated COX deficiency are involved in the maturation and assembly of COX, emphasizing the major role of such genes in COX pathology.

Similar articles

• 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.

  Antonicka H, Leary SC, Guercin GH, Agar JN, Horvath R, Kennaway NG, Harding CO, Jaksch M, Shoubridge EA. Antonicka H, et al. Hum Mol Genet. 2003 Oct 15;12(20):2693-702. doi: 10.1093/hmg/ddg284. Epub 2003 Aug 19. Hum Mol Genet. 2003. PMID: 12928484

• Isolation of a human cDNA for heme A:farnesyltransferase by functional complementation of a yeast cox10 mutant.

  Glerum DM, Tzagoloff A. Glerum DM, et al. Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8452-6. doi: 10.1073/pnas.91.18.8452. Proc Natl Acad Sci U S A. 1994. PMID: 8078902 Free PMC article.

• Mutations of the SCO1 gene in mitochondrial cytochrome c oxidase deficiency with neonatal-onset hepatic failure and encephalopathy.

  Valnot I, Osmond S, Gigarel N, Mehaye B, Amiel J, Cormier-Daire V, Munnich A, Bonnefont JP, Rustin P, Rötig A. Valnot I, et al. Am J Hum Genet. 2000 Nov;67(5):1104-9. doi: 10.1016/S0002-9297(07)62940-1. Epub 2000 Sep 28. Am J Hum Genet. 2000. PMID: 11013136 Free PMC article.

• Genetic defects of cytochrome c oxidase assembly.

  Pecina P, Houstková H, Hansíková H, Zeman J, Houstek J. Pecina P, et al. Physiol Res. 2004;53 Suppl 1:S213-23. Physiol Res. 2004. PMID: 15119951 Review.

• Defects in the biosynthesis of mitochondrial heme c and heme a in yeast and mammals.

  Moraes CT, Diaz F, Barrientos A. Moraes CT, et al. Biochim Biophys Acta. 2004 Dec 6;1659(2-3):153-9. doi: 10.1016/j.bbabio.2004.09.002. Biochim Biophys Acta. 2004. PMID: 15576047 Review.

Cited by

• Novel transporter required for biogenesis of cbb3-type cytochrome c oxidase in Rhodobacter capsulatus.

  Ekici S, Yang H, Koch HG, Daldal F. Ekici S, et al. mBio. 2012 Jan 31;3(1):e00293-11. doi: 10.1128/mBio.00293-11. Print 2012. mBio. 2012. PMID: 22294680 Free PMC article.

• Large-scale deletion and point mutations of the nuclear NDUFV1 and NDUFS1 genes in mitochondrial complex I deficiency.

  Bénit P, Chretien D, Kadhom N, de Lonlay-Debeney P, Cormier-Daire V, Cabral A, Peudenier S, Rustin P, Munnich A, Rötig A. Bénit P, et al. Am J Hum Genet. 2001 Jun;68(6):1344-52. doi: 10.1086/320603. Epub 2001 May 7. Am J Hum Genet. 2001. PMID: 11349233 Free PMC article.

• Transduction of human recombinant proteins into mitochondria as a protein therapeutic approach for mitochondrial disorders.

  Papadopoulou LC, Tsiftsoglou AS. Papadopoulou LC, et al. Pharm Res. 2011 Nov;28(11):2639-56. doi: 10.1007/s11095-011-0546-y. Epub 2011 Aug 27. Pharm Res. 2011. PMID: 21874377 Review.

• From Synthesis to Utilization: The Ins and Outs of Mitochondrial Heme.

  Swenson SA, Moore CM, Marcero JR, Medlock AE, Reddi AR, Khalimonchuk O. Swenson SA, et al. Cells. 2020 Feb 29;9(3):579. doi: 10.3390/cells9030579. Cells. 2020. PMID: 32121449 Free PMC article. Review.

• Biosynthesis and trafficking of heme o and heme a: new structural insights and their implications for reaction mechanisms and prenylated heme transfer.

  Rivett ED, Heo L, Feig M, Hegg EL. Rivett ED, et al. Crit Rev Biochem Mol Biol. 2021 Dec;56(6):640-668. doi: 10.1080/10409238.2021.1957668. Epub 2021 Aug 25. Crit Rev Biochem Mol Biol. 2021. PMID: 34428995 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Silverchair Information Systems

• Molecular Biology Databases

  • BioCyc
  • Gene Ontology
  • GlyGen glycoinformatics resource
  • Saccharomyces Genome Database