title: Demethoxy-Q, an intermediate of coenzyme Q biosynthesis, fails to support respiration in Saccharomyces cerevisiae and lacks antioxidant activity.
abstract: Caenorhabditis elegans clk-1 mutants cannot produce coenzyme Q(9) and instead accumulate demethoxy-Q(9) (DMQ(9)). DMQ(9) has been proposed to be responsible for the extended lifespan of clk-1 mutants, theoretically through its enhanced antioxidant properties and its decreased function in respiratory chain electron transport. In the present study, we assess the functional roles of DMQ(6) in the yeast Saccharomyces cerevisiae. Three mutations designed to mirror the clk-1 mutations of C. elegans were introduced into COQ7, the yeast homologue of clk-1: E233K, predicted to disrupt the di-iron carboxylate site considered essential for hydroxylase activity; L237Stop, a deletion of 36 amino acid residues from the carboxyl terminus; and P175Stop, a deletion of the carboxyl-terminal half of Coq7p. Growth on glycerol, quinone content, respiratory function, and response to oxidative stress were analyzed in each of the coq7 mutant strains. Yeast strains lacking Q(6) and producing solely DMQ were respiratory deficient and unable to support (6)either NADH-cytochrome c reductase or succinate-cytochrome c reductase activities. DMQ(6) failed to protect cells against oxidative stress generated by H(2)O(2) or linolenic acid. Thus, in the yeast model system, DMQ does not support respiratory activity and fails to act as an effective antioxidant. These results suggest that the life span extension observed in the C. elegans clk-1 mutants cannot be attributed to the presence of DMQ per se.
authors.affiliation: Centro Andaluz de Biologia del Desarrollo, Universidad Pablo de Olavide, 41013-Sevilla, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Padilla
authors.forename: Tanya
authors.initials: T
authors.lastname: Jonassen
authors.forename: María A
authors.initials: MA
authors.lastname: Jiménez-Hidalgo
authors.forename: Daniel José M
authors.initials: DJ
authors.lastname: Fernández-Ayala
authors.forename: Guillermo
authors.initials: G
authors.lastname: López-Lluch
authors.forename: Beth
authors.initials: B
authors.lastname: Marbois
authors.forename: Plácido
authors.initials: P
authors.lastname: Navas
authors.forename: Catherine F
authors.initials: CF
authors.lastname: Clarke
authors.forename: Carlos
authors.initials: C
authors.lastname: Santos-Ocaña
mesh_terms: D000483:Alleles; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D016227:Benzoquinones / Q000378:metabolism; D001665:Binding Sites; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D004579:Electron Transport; D005434:Flow Cytometry; D005990:Glycerol / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D013058:Mass Spectrometry; D008928:Mitochondria / Q000378:metabolism; D008956:Models, Chemical; D009154:Mutation; D009245:NADH Dehydrogenase / Q000378:metabolism; D018384:Oxidative Stress; D010101:Oxygen Consumption; D010455:Peptides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014451:Ubiquinone / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics*; D017962:alpha-Linolenic Acid / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D016227:Benzoquinones; D010455:Peptides; D017962:alpha-Linolenic Acid; D013481:Superoxides; D014451:Ubiquinone; C004532:quinone; D006861:Hydrogen Peroxide; D009245:NADH Dehydrogenase; D005990:Glycerol; C030777:ubiquinone 7