MCB Accepts, published online ahead of print on 19 October 2009

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Bestwick, M. Articles by Winge, D. R. PubMed PubMed Citation Articles by Bestwick, M. Articles by Winge, D. R.

 Previous Article  |  Next Article 

Mol. Cell. Biol. doi:10.1128/MCB.00869-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The Role of Coa2 in Hemylation of Yeast Cox1 Revealed by its Genetic Interaction with Cox10

Megan Bestwick, Oleh Khalimonchuk, Fabien Pierrel, and Dennis R. Winge^*

From the University of Utah Health Sciences Center, Departments of Medicine and Biochemistry, Salt Lake City, UT 84132

^* To whom correspondence should be addressed. Email: dennis.winge{at}hsc.utah.edu.

Sacccharomyces cerevisiae cells lacking the cytochrome c oxidase (CcO) assembly factor Coa2 are impaired in Cox1 maturation and exhibit a rapid degradation of newly synthesized Cox1. The respiratory deficiency of coa2 cells is suppressed by either the presence of a mutant allele of the Cox10 farnesyl transferase involved in heme a biosynthesis or through impaired proteolysis through the disruption of the mitochondrial Oma1 protease. Cox10 with a N196K substitution functions as a robust gain-of-function suppressor of the respiratory deficiency of coa2 cells, but lacks suppressor activity for two other CcO assembly mutant strains, coa1 and shy1. The suppressor activity of N196K mutant Cox10 is dependent on its catalytic function and the presence of Cox15, the second enzyme involved in heme a biosynthesis. Varying the substitution at Asn196 reveals a correlation between the suppressor activity and the stabilization of the high mass homo-oligomeric Cox10 complex. We postulate that the mutant Cox10 complex has enhanced efficiency in the addition of heme a to Cox1. Coa2 appears to impart stability to the oligomeric wild-type Cox10 complex involved in Cox1 hemylation.