The C. elegans Opa1 homologue EAT-3 is essential for resistance to free radicals

PLoS Genet. 2008 Feb 29;4(2):e1000022. doi: 10.1371/journal.pgen.1000022.

Abstract

The C. elegans eat-3 gene encodes a mitochondrial dynamin family member homologous to Opa1 in humans and Mgm1 in yeast. We find that mutations in the C. elegans eat-3 locus cause mitochondria to fragment in agreement with the mutant phenotypes observed in yeast and mammalian cells. Electron microscopy shows that the matrices of fragmented mitochondria in eat-3 mutants are divided by inner membrane septae, suggestive of a specific defect in fusion of the mitochondrial inner membrane. In addition, we find that C. elegans eat-3 mutant animals are smaller, grow slower, and have smaller broodsizes than C. elegans mutants with defects in other mitochondrial fission and fusion proteins. Although mammalian Opa1 is antiapoptotic, mutations in the canonical C. elegans cell death genes ced-3 and ced-4 do not suppress the slow growth and small broodsize phenotypes of eat-3 mutants. Instead, the phenotypes of eat-3 mutants are consistent with defects in oxidative phosphorylation. Moreover, eat-3 mutants are hypersensitive to paraquat, which promotes damage by free radicals, and they are sensitive to loss of the mitochondrial superoxide dismutase sod-2. We conclude that free radicals contribute to the pathology of C. elegans eat-3 mutants.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Drug Resistance / genetics
  • Dynamins / chemistry
  • Dynamins / genetics
  • Dynamins / metabolism
  • Free Radicals / metabolism
  • Free Radicals / toxicity
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism
  • GTP-Binding Proteins / genetics
  • Genes, Helminth
  • Humans
  • Mitochondria / metabolism
  • Mitochondria / ultrastructure
  • Mitochondrial Proteins / genetics
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Optic Atrophy, Autosomal Dominant / etiology
  • Optic Atrophy, Autosomal Dominant / genetics
  • Optic Atrophy, Autosomal Dominant / metabolism
  • Oxidative Phosphorylation
  • Paraquat / toxicity
  • Phenotype
  • RNA Interference
  • Saccharomyces cerevisiae Proteins / genetics
  • Sequence Homology, Amino Acid
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Free Radicals
  • MGM1 protein, S cerevisiae
  • Mitochondrial Proteins
  • Saccharomyces cerevisiae Proteins
  • Superoxide Dismutase
  • superoxide dismutase 2
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • OPA1 protein, human
  • Dyn-1 protein, C elegans
  • Dynamins
  • Paraquat