1. Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan
2. Department of Biochemistry, Kihara Institute for Biological Research, Yokohama City University, Totsuka, Yokohama, Kanagawa 244-0813, Japan
3. Department of Biology, Texas Christian University, Fort Worth, Texas 76129, USA
4. Tokyo Research Laboratory, Kyowa Hakko Kogyo Co. Ltd., Machida, Tokyo 194-8533, Japan

Correspondence to: Naoaki Ishii¹ Correspondence and requests for materials should be addressed to N.I. (e-mail: Email: nishii@is.icc.u-tokai.ac.jp).

Abstract

Much attention has focused on the aetiology of oxidative damagein cellular and organismal ageing^{1, 2, 3, 4}. Especially toxic arethe reactive oxygen byproducts of respiration and other biological processes⁵. A mev-1 (kn1 ) mutant of Caenorhabditis elegans has been found to be hypersensitive to raised oxygen concentrations⁶,⁷. Unlike the wild type, its lifespan decreases dramatically as oxygen concentrations are increased from 1 to 60% (ref. 7). Strains bearing this mutation accumulate markers of ageing (such as fluorescent materials and protein carbonyls) faster than the wild type⁸,⁹. 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-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.