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

Nature volume 394, pages 694–697 (1998)Cite this article

Abstract

Much attention has focused on the aetiology of oxidative damagein cellular and organismal ageing1,2,3,4. 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.

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Figure 1: Genetic, physical and functional maps of the mev-1 region.
Figure 2: Comparison of oxygen sensitivity and lifespans of wild-type (N2), mev-1 (kn1 ) and rescued transgenic animals (kn1;knIs2 )
Figure 3: Comparison of the predicted amino-acid sequences of Celegans cyt-1 (mev-1 ), bovine and human cytochrome b 560.

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Acknowledgements

We thank M. Hengartner for strains and for suggestions that facilitated the mapping of mev-1 . The wild-type strain was from the C. elegans Genetics Center, which is supported by the National Center for Research Resources (NCRR). This work was supported by Tokai University School of Medicine Research Project and by a Grant in Aid for Aging Research from the Ministry of Human and Welfare, Japan, and for Scientific Research from the Ministry of Education, Science, Sports and Culture, Japan.

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Authors and Affiliations

  1. Department of Molecular Life Science, Tokai University School of Medicine, Isehara, 259-1193, Kanagawa, Japan

    Naoaki Ishii, Michio Tsuda, Kayo Yasuda, Nanami Senoo-Matsuda, Sumino Yanase & Kenshi Suzuki

  2. Department of Biochemistry, Kihara Institute for Biological Research, Yokohama City University, Totsuka, Kanagawa, 244-0813, Yokohama, Japan

    Michihiko Fujii & Dai Ayusawa

  3. Department of Biology, Texas Christian University, Fort Worth, 76129, Texas, USA

    Philip S. Hartman

  4. Tokyo Research Laboratory, Kyowa Hakko Kogyo Co. Ltd., Machida, 194-8533, Tokyo, Japan

    Nanami Senoo-Matsuda

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  1. Naoaki Ishii
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Correspondence to Naoaki Ishii.

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Ishii, N., Fujii, M., Hartman, P. et al. A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes. Nature 394, 694–697 (1998). https://doi.org/10.1038/29331

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