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

Nature. 1998 Aug 13;394(6694):694-7. doi: 10.1038/29331.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / genetics
  • Aging / physiology*
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / enzymology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Chromosome Mapping
  • Cytochrome b Group / genetics
  • Cytochrome b Group / physiology*
  • Electron Transport
  • Electron Transport Complex II*
  • Humans
  • Molecular Sequence Data
  • Oxidative Stress*
  • Point Mutation
  • Sequence Homology, Amino Acid
  • Succinate Cytochrome c Oxidoreductase / genetics
  • Succinate Cytochrome c Oxidoreductase / physiology*
  • Ubiquinone / metabolism

Substances

  • Cytochrome b Group
  • Ubiquinone
  • cytochrome b560
  • Succinate Cytochrome c Oxidoreductase
  • Electron Transport Complex II

Associated data

  • GENBANK/H83619
  • GENBANK/L26545
  • GENBANK/N34060
  • GENBANK/R87065
  • GENBANK/S74803