Ishii N, Fujii M, Hartman P S, Tsuda M, Yasuda K, Senoo-Matsuda N, Yanase S, Ayusawa D, Suzuki K
Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Nature. 1998 Aug 13;394(6694):694-7. doi: 10.1038/29331.
Much attention has focused on the aetiology of oxidative damage in cellular and organismal ageing. Especially toxic are the reactive oxygen byproducts of respiration and other biological processes. A mev-1(kn1) mutant of Caenorhabditis elegans has been found to be hypersensitive to raised oxygen concentrations. Unlike the wild type, its lifespan decreases dramatically as oxygen concentrations are increased from 1 to 60%. Strains bearing this mutation accumulate markers of ageing (such as fluorescent materials and protein carbonyls) faster than the wild type. We show here that mev-1 encodes a subunit of the enzyme succinate dehydrogenase cytochrome b, which is a component of complex II of the mitochondrial electron transport chain. We found that the ability of complex II to catalyse electron transport from succinate to ubiquinone is compromised in mev-1 animals. This may cause an indirect increase in superoxide levels, which in turn leads to oxygen hypersensitivity and premature ageing. Our results indicate that mev-1 governs the rate of ageing by modulating the cellular response to oxidative stress.
许多关注聚焦于细胞和机体衰老过程中氧化损伤的病因。呼吸及其他生物过程产生的活性氧副产物尤其具有毒性。秀丽隐杆线虫的mev-1(kn1)突变体已被发现对升高的氧浓度高度敏感。与野生型不同，当氧浓度从1%增加到60%时，其寿命会显著缩短。携带这种突变的品系比野生型更快地积累衰老标记物（如荧光物质和蛋白质羰基）。我们在此表明，mev-1编码琥珀酸脱氢酶细胞色素b的一个亚基，该亚基是线粒体电子传递链复合体II的一个组分。我们发现，在mev-1动物中，复合体II催化琥珀酸到泛醌的电子传递的能力受损。这可能间接导致超氧化物水平升高，进而导致氧超敏反应和早衰。我们的结果表明，mev-1通过调节细胞对氧化应激的反应来控制衰老速率。
