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

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

Abstract: 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.

Keywords: Aging/genetics/*physiology; Amino Acid Sequence; Animals; Animals, Genetically Modified; Caenorhabditis elegans/enzymology/genetics/*physiology; Chromosome Mapping; Cytochrome b Group/genetics/*physiology; Electron Transport; *Electron Transport Complex II; Humans; Molecular Sequence Data; *Oxidative Stress; Point Mutation; Sequence Homology, Amino Acid; Succinate Cytochrome c Oxidoreductase/genetics/*physiology; Ubiquinone/metabolism
Journal: Nature
Volume: 394
Issue: 6694
Pages: 694-7
Date: Aug. 26, 1998
PMID: 9716135
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Citation:

Ishii N, Fujii M, Hartman PS, Tsuda M, Yasuda K, Senoo-Matsuda N, Yanase S, Ayusawa D, Suzuki K (1998) A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes. Nature 394: 694-7.


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