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J. Biol. Chem., Vol. 278, Issue 28, 25308-25316, July 11, 2003

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The Saccharomyces cerevisiae COQ6 Gene Encodes a Mitochondrial Flavin-dependent Monooxygenase Required for Coenzyme Q Biosynthesis^*

Peter Gin , Adam Y. Hsu , Steven C. Rothman  , Tanya Jonassen , Peter T. Lee , Alexander Tzagoloff ¶ and Catherine F. Clarke  ||

From the Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, California 90095 and the ^¶Department of Biological Sciences, Columbia University, New York, New York 10027

Coenzyme Q (Q) is a lipid that functions as an electron carrier in the mitochondrial respiratory chain in eukaryotes. There are eight complementation groups of Q-deficient Saccharomyces cerevisiae mutants, designated coq1–coq8. Here we have isolated the COQ6 gene by functional complementation and, in contrast to a previous report, find it is not an essential gene. coq6 mutants are unable to grow on nonfermentable carbon sources and do not synthesize Q but instead accumulate the Q biosynthetic intermediate 3-hexaprenyl-4-hydroxybenzoic acid. The Coq6 polypeptide is imported into the mitochondria in a membrane potential-dependent manner. Coq6p is a peripheral membrane protein that localizes to the matrix side of the inner mitochondrial membrane. Based on sequence homology to known proteins, we suggest that COQ6 encodes a flavin-dependent monooxygenase required for one or more steps in Q biosynthesis.

Received for publication, March 28, 2003

^* This work was supported in part by National Institutes of Health Grants GM45952 (to C. F. C.) and HL2274 (to A. T.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: Dept. of Chemistry, University of Utah, 315 South 1400 E, Salt Lake City, UT 84112-0850.

^|| To whom correspondence should be addressed: Dept. of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Dr. East, Los Angeles, CA 90095-1569. Tel.: 310-825-0771; Fax: 310-206-5213; E-mail: cathy{at}mbi.ucla.edu.

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