A MUTATION IN SUCCINATE-DEHYDROGENASE CYTOCHROME-B CAUSES OXIDATIVE STRESS AND AGING IN NEMATODES

Much attention has focused on the aetiology of oxidative damage in cel lular and organismal ageing(1-4). Especially toxic are the reactive ox ygen byproducts of respiration and other biological processes(5). A me v-1(kn1) mutant of Caenorhabditis elegans has been found to be hyperse nsitive to raised oxygen concentrations(6,7), Unlike the wild type, it s lifespan decreases dramatically as oxygen concentrations are increas ed from 1 tee 60% (ref. 7). Strains bearing this mutation accumulate m arkers of ageing (such as fluorescent materials and protein carbonyls) faster than the wild type(8,9). We show here that mev-1 encodes a sub unit of the enzyme succinate dehydrogenase cytochrome b, which is a co mponent of complex II of the mitochondrial electron transport chain. W e 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 respo nse to oxidative stress.