Cmc1p is a Conserved Mitochondrial Twin Cx₉C Protein Involved in Cytochrome c Oxidase Biogenesis

Department of Biochemistry & Molecular Biology, Department of Neurology. The John T. MacDonald Foundation Center for Medical Genetics. University of Miami Miller School of Medicine. Miami, FL

^* To whom correspondence should be addressed. Email: abarrientos{at}med.miami.edu.

	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 chaperons 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.