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

Abstract

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 flavindependent monooxygenase required for one or more steps in Q biosynthesis.

Coenzyme Q supplementation or Over-Expression of the Yeast Coq8 Putative Kinase Stabilizes Multi-Subunit Coq Polypeptide Complexes in Yeast Coq Null Mutants

“…Cytochrome c, which peripherally attaches to the inner mitochondrial membrane through electrostatic interactions with fatty acids and acidic phospholipids [65], was released from the sonicated mitoplasts following salt addition, as expected. These results provide further support for the submitochondrial localization data indicating that yeast Coq7 is a peripheral membrane protein on the matrix side as are Coq1, Coq3, Coq4, Coq5, Coq6, Coq8, and Coq9 polypeptides [20,31,36,49,[66][67][68].…”

Genetic Evidence for a Multi-subunit Complex in Coenzyme Q Biosynthesis in Yeast and the Role of the Coq1 Hexaprenyl Diphosphate Synthase

“…3d). Therefore, Coq1p is a peripheral inner membrane protein on the matrix side as are Coq3p, Coq4p, Coq5p, and Coq6p (21,(27)(28)(29).…”

“…Immunoblot Analysis-Immunoblot analysis was performed as described previously (27). Primary antibodies were used at the following concentrations: anti-Coq1p, 1:10,000; anti-Coq3p, 1:1000; anti-Coq4p, 1:1000; anti-Coq5p, 1:1000; anti-Coq6p, 1:500; anti-␤-subunit of F 1 -ATPase, 1:10,000; anti-cytochrome c 1 , 1:1000; anti-cytochrome c, 1:10,000; anti-cytochrome b 2 , 1:1000; and anti-Hsp60p, 1:10,000.…”

Coq3 and Coq4 Define a Polypeptide Complex in Yeast Mitochondria for the Biosynthesis of Coenzyme Q

“…Of the eight proteins involved in the biosynthesis of Q in S. cerevisiae, five have been identified as mitochondrial matrix proteins peripherally associated with the inner membrane (18,25,(27)(28)(29). Submitochondrial localization of a hemagglutinintagged Coq7 fusion protein identified it as an integral membrane protein of the mitochondrial inner membrane (30), and it is hypothesized to be an interfacial membrane protein (31).…”