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Molecular and Cellular Biology, July 2008, p. 4354-4364, Vol. 28, No. 13
0270-7306/08/$08.00+0     doi:10.1128/MCB.01920-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Cmc1p Is a Conserved Mitochondrial Twin CX9C Protein Involved in Cytochrome c Oxidase Biogenesis{triangledown} ,{dagger}

Darryl Horn,1 Hassan Al-Ali,1 and Antoni Barrientos1,2*

Department of Biochemistry & Molecular Biology,1 Department of Neurology, The John T. MacDonald Foundation Center for Medical Genetics, University of Miami Miller School of Medicine, Miami, Florida2

Received 24 October 2007/ Returned for modification 3 December 2007/ Accepted 24 March 2008

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.


* Corresponding author. Mailing address: Departments of Neurology and Biochemistry & Molecular Biology, The John T. Macdonald Center for Medical Genetics, University of Miami Miller School of Medicine, 1600 N.W. 10th Ave., RMSB # 2067, Miami, FL 33136. Phone: (305) 243-8683. Fax: (305) 243-3914. E-mail: abarrientos{at}med.miami.edu

{triangledown} Published ahead of print on 28 April 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.


Molecular and Cellular Biology, July 2008, p. 4354-4364, Vol. 28, No. 13
0270-7306/08/$08.00+0     doi:10.1128/MCB.01920-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.







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