Function analysis of the gene of an oxygen-dependent short life-scan mutant.

氧化损伤促进细胞和生物体衰老的假说受到了广泛关注。一个mev-1（kn 1）突变体的线虫秀丽隐杆线虫分离的基础上，其甲基紫精（百草枯）的超敏性，也被证明是高氧过敏。与野生型不同，当氧气浓度从1%增加到60%时，其寿命急剧下降。携带这种突变的菌株积累荧光物质和蛋白质羰基，老化的标志，比野生型更快的速度。我们通过转化拯救法克隆了mev-1基因，发现它是先前测序的编码琥珀酸脱氢酶细胞色素B的基因（cyt-1）。kn 1等位基因是一个错义突变，废除复合物II活性的线粒体膜，但不是琥珀酸脱氢酶活性本身。在mev-1动物中有两组重要的生化变化可以解释这两种表型：1）超氧阴离子的过量产生和谷胱甘肽含量的相互减少; 2）可能导致乳酸酸中毒的能量代谢异常。这些数据表明，Cyt-1在能量代谢和保护免受氧化应激中起着重要作用。

Much attention has been focused on the hypothesis that oxidative damage contributes to cellular and organismal aging. A mev-1 (kn1) mutant of the nematode Caenorhabditis elegans was isolated on the basis of its methyl viologen (paraquat) hypersensitivity and was also shown to be hypersensitive to hyperoxia. Unlike with wild type, its life span decreased dramatically as oxygen concentrations were increased from 1% to 60%. Strains bearing this mutation accumulated fluorescent materials and protein carbonyl groups, markers of aging, at faster rates than the wild type. We cloned mev-1 gene by transformation rescue and found that it is the previously sequenced gene (cyt-1) that encodes succinate dehydrogenase cytochrome b. The kn1 allele is a missense mutation that abolished complex II activity in the mitochondrial membrane but not succinate dehydrogenase enzyme activity per se. There are two important sets of biochemical changes in mev-1 animals that serve to explain these two phenotypes : 1) an overproduction of superoxide anion and a reciprocal reduction in glutathione content ; and 2) abnormalities in energy metabolism that likely lead to lactic acidosis. These data indicate that Cyt-1 plays an important role in the energy metabolism and protection from the oxidative stress.