COQ9, a New Gene Required for the Biosynthesis of Coenzyme Q in Saccharomyces cerevisiae

Abstract

Currently, eight genes are known to be involved in coenzyme Q 6 biosynthesis in Saccharomyces cerevisiae. Here, we report a new gene designated COQ9 that is also required for the biosynthesis of this lipoid quinone. The respiratory-deficient pet mutant C92 was found to be deficient in coenzyme Q and to have low mitochondrial NADH-cytochrome c reductase activity, which could be restored by addition of coenzyme Q 2 . The mutant was used to clone COQ9, corresponding to reading frame YLR201c on chromosome XII. The respiratory defect of C92 is complemented by COQ9 and suppressed by COQ8/ ABC1. The latter gene has been shown to be required for coenzyme Q biosynthesis in yeast and bacteria. Suppression by COQ8/ABC1 of C92, but not other coq9 mutants tested, has been related to an increase in the mitochondrial concentration of several enzymes of the pathway. Coq9p may either catalyze a reaction in the coenzyme Q biosynthetic pathway or have a regulatory role similar to that proposed for Coq8p.Biosynthesis of coenzyme Q (ubiquinone) in eukaryotes occurs in mitochondria. Eight genes designated COQ1-8 have been shown to be involved in the biosynthesis of this lipoid component of the electron transport chain of Saccharomyces cerevisiae (1). The products of these genes have been localized to the inner membrane (2-8) and, in some cases, were inferred to be present in a complex (4, 9, 10). The chemical intermediates detected in some mutants have revealed that the pathways in bacteria and in this yeast are identical up to the formation of 3-hexaprenyl-4-hydroxybenzoic acid (HHB) 1 (11,12), at which point they diverge for the next three steps, but then converge again in the last stages of biosynthesis (11,12).A hallmark of most yeast coq mutants is the accumulation of HHB when the biochemical block occurs at any step subsequent to the formation of this early intermediate (5-8, 13, 14). This may indicate that 1) most intermediates of the pathway are unstable and degraded; 2) the pathway is highly regulated; or 3) the enzymes are organized in a complex, which is highly sensitive to mutations in any one of its components. The latter possibility is supported by recent evidence indicating an interdependence of some Coq proteins for their stability (4). Most of the COQ gene products have been related to specific reactions of the eukaryotic pathway based on their homology to the bacterial counterparts (6, 7). The reactions catalyzed by the products of COQ4 and COQ8/ABC1, however, still need to be clarified (5,8).In the course of analyzing the biochemical defects of respiratory-deficient pet mutants of S. cerevisiae, we have identified a new gene that, when mutated, produces a phenotype similar to that of coenzyme Q mutants. This gene is defined by complementation group G61 of our pet mutant collection (1) and has been named COQ9. Homologs of COQ9 are present in a wide range of different eukaryotes, but not in bacteria, indicating that its function is specific to coenzyme Q biosynthesis in mitochondria. Suppression of a coq9 mutant by C...

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Identification of Coq11, a New Coenzyme Q Biosynthetic Protein in the CoQ-Synthome in Saccharomyces cerevisiae

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