Do T Q, Schultz J R, Clarke C F
Department of Chemistry and Biochemistry, University of California, Los Angeles 90095-1569, USA.
Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7534-9. doi: 10.1073/pnas.93.15.7534.
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.
辅酶Q（泛醌或Q）在呼吸链中发挥着众所周知的电子传递功能，最近的证据表明，泛醌的还原形式（QH2）可能作为一种有效的脂溶性抗氧化剂发挥第二种作用。为了探究QH2在体内作为抗氧化剂的功能，我们利用了一种酿酒酵母的Q缺陷菌株，该菌株的COQ3基因存在缺失[克拉克，C.F.，威廉姆斯，W.和照屋，J.H.（1991年）《生物化学杂志》266，16636 - 16644]。Q缺陷酵母和野生型亲本菌株用多不饱和脂肪酸处理，多不饱和脂肪酸容易发生自氧化并分解成有毒产物。在本研究中，我们发现Q缺陷酵母对亚麻酸和其他多不饱和脂肪酸的自氧化产物高度敏感。相比之下，对自氧化分解有抗性的单不饱和油酸则没有影响。单个拷贝质粒上存在COQ3基因可防止coq3delta菌株的超敏反应，这表明敏感表型完全是由于无法产生Q所致。与野生型或呼吸缺陷对照菌株相比，多不饱和脂肪酸处理导致coq3突变体中脂质氢过氧化物显著升高。添加丁基羟基甲苯、α - 生育酚或水溶性维生素E类似物trolox可挽救Q缺陷突变体的超敏反应。结果表明，多不饱和脂肪酸的自氧化产物介导细胞杀伤，并且QH2在体内对保护真核细胞免受这些产物的影响方面发挥着重要作用。
