A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes
A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes
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DOI：
10.1038/29331
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发表时间：
1998-08-13
期刊：
影响因子：
64.8
通讯作者：
Suzuki, K
中科院分区：
文献类型：
--
作者：
Ishii, N;Fujii, M;Suzuki, K
许多注意力都集中在细胞和有机体老化中氧化损伤的病因学上（1-4）。特别有毒的是呼吸和其他生物过程的活性氧副产品（5）。已发现秀丽隐杆线虫的mev-1（kn 1）突变体对升高的氧浓度超敏感（6，7）。与野生型不同，当氧浓度从1 tee增加60%时，其寿命急剧下降（参考文献7）。携带这种突变的菌株比野生型更快地积累老化标记物（如荧光物质和蛋白质羰基）（8，9）。我们在这里显示，mev-1编码的酶琥珀酸脱氢酶细胞色素B，这是线粒体电子传递链的复合物II的组成部分的一个亚基。我们发现，复合物II的能力，以催化电子传递从琥珀酸泛醌在MEV-1动物受到损害。这可能会导致超氧化物水平的间接增加，从而导致氧过敏和过早衰老。我们的研究结果表明mev-1通过调节细胞对氧化应激的反应来控制衰老的速度。
Much attention has focused on the aetiology of oxidative damage in cellular and organismal ageing(1-4). Especially toxic are the reactive oxygen byproducts of respiration and other biological processes(5). A mev-1(kn1) mutant of Caenorhabditis elegans has been found to be hypersensitive to raised oxygen concentrations(6,7), Unlike the wild type, its lifespan decreases dramatically as oxygen concentrations are increased from 1 tee 60% (ref. 7). Strains bearing this mutation accumulate markers of ageing (such as fluorescent materials and protein carbonyls) faster than the wild type(8,9). 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-l 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.