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.AD - Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan. nishii@is.icc.u-tokai.ac.jpFAU - Ishii, NAU - Ishii NFAU - Fujii, MAU - Fujii MFAU - Hartman, P SAU - Hartman PSFAU - Tsuda, MAU - Tsuda MFAU - Yasuda, KAU - Yasuda KFAU - Senoo-Matsuda, NAU - Senoo-Matsuda NFAU - Yanase, SAU - Yanase SFAU - Ayusawa, DAU - Ayusawa DFAU - Suzuki, KAU - Suzuki KLA - engSI - GENBANK/H83619SI - GENBANK/L26545SI - GENBANK/N34060SI - GENBANK/R87065SI - GENBANK/S74803PT - Journal ArticleCY - ENGLANDTA - NatureJID - 0410462RN - 1339-63-5 (Ubiquinone)RN - 37337-51-2 (cytochrome
b560)RN - 9035-37-4 (Cytochrome b)RN - EC 1.- (Succinate Cytochrome c Oxidoreductase)SB - IM