CGC Bibliography Paper 3157

A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes.

Ishii N, Fujii M, Hartman PS, Tsuda M, Yasuda K, Senoo-Matsuda N, Yanase S, Ayusawa D, Suzuki K

Medline:
98379992
Citation:
Nature 394: 694-697 1998
Type:
ARTICLE
Genes:
ced-9 cyt-1 mev-1
Abstract:
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