RRC ID 4249
Author Kanazawa T, Zappaterra MD, Hasegawa A, Wright AP, Newman-Smith ED, Buttle KF, McDonald K, Mannella CA, van der Bliek AM.
Title The C. elegans Opa1 homologue EAT-3 is essential for resistance to free radicals.
Journal PLoS Genet.
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.
Volume 4(2)
Pages e1000022
Published 2008-2-29
DOI 10.1371/journal.pgen.1000022
PMID 18454199
PMC PMC2265488
MeSH 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
IF 5.224
Times Cited 66
C.elegans tm1107 tm1133