Enhanced sensitivity of ubiquinone-deficient mutants of Saccharomyces cerevisiae to products of autoxidized polyunsaturated fatty acids.
Coenzyme Q (ubiquinone or Q) plays a well known electron transport function in the respiratory chain, and recent evidence suggests that the reduced form of ubiquinone (QH2) may play a second role as a potent lipid-soluble antioxidant. To probe the function of QH2 as an antioxidant in vivo, we have made use of a Q-deficient strain of Saccharomyces cerevisiae harboring a deletion in the COQ3 gene [Clarke, C. F., Williams, W. & Teruya, J. H. (1991) J. Biol. Chem. 266, 16636-16644]. Q-deficient yeast and the wild-type parental strain were subjected to treatment with polyunsaturated fatty acids, which are prone to autoxidation and breakdown into toxic products. In this study we find that Q-deficient yeast are hypersensitive to the autoxidation products of linolenic acid and other polyunsaturated fatty acids. In contrast, the monounsaturated oleic acid, which is resistant to autoxidative breakdown, has no effect. The hypersensitivity of the coq3delta strains can be prevented by the presence of the COQ3 gene on a single copy plasmid, indicating that the sensitive phenotype results solely from the inability to produce Q. As a result of polyunsaturated fatty acid treatment, there is a marked elevation of lipid hydroperoxides in the coq3 mutant as compared with either wild-type or respiratory-deficient control strains. The hypersensitivity of the Q-deficient mutant can be rescued by the addition of butylated hydroxytoluene, alpha-tocopherol, or trolox, an aqueous soluble vitamin E analog. The results indicate that autoxidation products of polyunsaturated fatty acids mediate the cell killing and that QH2 plays an important role in vivo in protecting eukaryotic cells from these products.
Do
T Q
TQ
Department of Chemistry and Biochemistry, University of California, Los Angeles 90095-1569, USA.
Schultz
J R
JR
Clarke
C F
CF
D000975:Antioxidants / Q000494:pharmacology*; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology; D004579:Electron Transport; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005838:Genotype; D007700:Kinetics; D008054:Lipid Peroxides; D019301:Oleic Acid / Q000494:pharmacology; D010084:Oxidation-Reduction; D010957:Plasmids; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013045:Species Specificity; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014451:Ubiquinone / Q000235:genetics / Q000378:metabolism*; D014810:Vitamin E / Q000494:pharmacology; D017962:alpha-Linolenic Acid / Q000494:pharmacology*
D000975:Antioxidants; D002839:Chromans; D005231:Fatty Acids, Unsaturated; D008054:Lipid Peroxides; D017392:Thiobarbituric Acid Reactive Substances; D017962:alpha-Linolenic Acid; D014451:Ubiquinone; D014810:Vitamin E; D002084:Butylated Hydroxytoluene; D019301:Oleic Acid; D013482:Superoxide Dismutase; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid