Yeast Clk-1 Homologue (Coq7/Cat5) Is a Mitochondrial Protein in Coenzyme Q Synthesis

Abstract

Mutations in the clk-1 gene result in slower development and increased life span in Caenorhabditis elegans. The Saccharomyces cerevisiae homologue COQ7/CAT5 is essential for several metabolic pathways including ubiquinone biosynthesis, respiration, and gluconeogenic gene activation. We show here that Coq7p/Cat5p is a mitochondrial inner membrane protein directly involved in ubiquinone biosynthesis, and that the defect in gluconeogenic gene activation in coq7/cat5 null mutants is a general consequence of a defect in respiration. These results obtained in the yeast model suggest that the effects on development and life span in C. elegans clk-1 mutants may relate to changes in the amount of ubiquinone, an essential electron transport component and a lipid soluble antioxidant.

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

“…Similar to Coq2p, Coq3p, Coq4p, Coq5p, Coq7p, and Coq8p/Abc1p, the Coq6 polypeptide is imported into mitochondria (14). In agreement with submitochondrial localization studies of Coq1p, Coq3p, Coq4p, Coq5p, and Coq7p, Coq6p is localized to the matrix side of the inner membrane (18,40,50). 2 S. cerevisiae is a facultative anaerobe capable of fermentation and aerobic respiration, and none of the other COQ genes have been identified as being essential.…”

Reproductive Fitness and Quinone Content of Caenorhabditis elegans clk-1 Mutants Fed Coenzyme Q Isoforms of Varying Length

“…There was slightly more Q 8 than Q 7 assimilated from the diet in the N2 animals, 101 Ϯ 6 pmol Q 8 per mg protein versus 65 Ϯ 5 pmol Q 7 per mg protein. The mutant strains clk-1(e2519) and clk-1(qm30) similarly accumulated Q 7 and Q 8 from their respective diets, in addition to the endogenously synthesized DMQ 9 and RQ 9 . In three separate experiments, the levels of DMQ 9 did not show a consistent trend when the animals were fed either food.…”

“…C. elegans with mutations in the clk-1 gene, the COQ7 homologue, show slowed adult behaviors, including defecation cycles and pharyngeal pumping, slowed embryonic and post-embryonic development, and decreased brood sizes (11,12). These animals were found to accumulate DMQ 9 , the expected biosynthetic intermediate, and a small amount of Q 8 , incorporated from their E. coli diet (13,14). When clk-1 worms are fed GD1, a Q-less E. coli, they arrest at the L2 larval stage if fed from hatching or develop into sterile adults if fed GD1 as dauer larvae (14).…”

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

“…6B). [12,26,37,50,69]. We were able to rescue the growth of each of the coq1-coq9 null mutants on YPEG medium containing ethanol and glycerol as non-fermentable carbon sources, with the addition of 2 µM Q 6 to the medium (data not shown).…”