title: Cmc1p is a conserved mitochondrial twin CX9C protein involved in cytochrome c oxidase biogenesis.
abstract: Copper is an essential cofactor of two mitochondrial enzymes: cytochrome c oxidase (COX) and Cu-Zn superoxide dismutase (Sod1p). Copper incorporation into these enzymes is facilitated by metallochaperone proteins which probably use copper from a mitochondrial matrix-localized pool. Here we describe a novel conserved mitochondrial metallochaperone-like protein, Cmc1p, whose function affects both COX and Sod1p. In Saccharomyces cerevisiae, Cmc1p localizes to the mitochondrial inner membrane facing the intermembrane space. Cmc1p is essential for full expression of COX and respiration, contains a twin CX9C domain conserved in other COX assembly copper chaperones, and has the ability to bind copper(I). Additionally, mutant cmc1 cells display increased mitochondrial Sod1p activity, while CMC1 overexpression results in decreased Sod1p activity. Our results suggest that Cmc1p could play a direct or indirect role in copper trafficking and distribution to COX and Sod1p.
authors.affiliation: Department of Biochemistry & Molecular Biology, The John T. MacDonald Foundation Center for Medical Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Darryl
authors.initials: D
authors.lastname: Horn
authors.forename: Hassan
authors.initials: H
authors.lastname: Al-Ali
authors.forename: Antoni
authors.initials: A
authors.lastname: Barrientos
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D017124:Conserved Sequence; D003300:Copper / Q000494:pharmacology; D003576:Electron Transport Complex IV / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D056511:Metallochaperones; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000201:enzymology; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: C529981:CMC1 protein, S cerevisiae; D002352:Carrier Proteins; D056511:Metallochaperones; D024101:Mitochondrial Proteins; D050505:Mutant Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D003300:Copper; D013482:Superoxide Dismutase; D003576:Electron Transport Complex IV