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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Carrier Proteins / chemistry
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Carrier Proteins / isolation & purification
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Carrier Proteins / metabolism*
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Conserved Sequence*
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Copper / pharmacology
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Electron Transport Complex IV / metabolism*
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HeLa Cells
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Humans
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Metallochaperones
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Mitochondria / drug effects
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Mitochondria / enzymology*
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Mitochondrial Membranes / drug effects
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Mitochondrial Membranes / enzymology
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Mitochondrial Proteins / chemistry
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Mitochondrial Proteins / isolation & purification
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Mitochondrial Proteins / metabolism*
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Molecular Sequence Data
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Molecular Weight
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Mutant Proteins / metabolism
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Mutation / genetics
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Protein Binding / drug effects
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Protein Structure, Tertiary
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Protein Transport / drug effects
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Recombinant Proteins / isolation & purification
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Recombinant Proteins / metabolism
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Saccharomyces cerevisiae / cytology
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Saccharomyces cerevisiae / drug effects
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Saccharomyces cerevisiae / enzymology*
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Saccharomyces cerevisiae Proteins / chemistry
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Saccharomyces cerevisiae Proteins / isolation & purification
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Saccharomyces cerevisiae Proteins / metabolism*
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Superoxide Dismutase / metabolism
Substances
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CMC1 protein, S cerevisiae
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Carrier Proteins
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Metallochaperones
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Mitochondrial Proteins
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Mutant Proteins
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Recombinant Proteins
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Saccharomyces cerevisiae Proteins
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Copper
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Superoxide Dismutase
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Electron Transport Complex IV