The C. elegans Opa1 Homologue EAT-3 Is Essential for Resistance to Free Radicals

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.

Coenzyme Q protects Caenorhabditis elegans GABA neurons from calcium-dependent degeneration

“…S8A). We also used double RNAi to test fzo-1, a gene required for mitochondrial fusion (41). In this case, fzo-1 knockdown actually enhances the GABA neuron degeneration phenotype of coq-1-deficient animals as expected for a treatment that impairs mitochondrial fusion (Fig.…”

Neural activity and CaMKII protect mitochondria from fragmentation in aging Caenorhabditis elegans neurons

“…Their C. elegans homologs are drp-1, fzo-1, and eat-3, respectively (28)(29)(30). We examined mitochondrial morphology in the drp-1 null mutant, and found that age-dependent mitochondrial fragmentation in the drp-1 mutant was similar to that of the wild type ( Fig.…”

Impaired complex IV activity in response to loss of LRPPRC function can be compensated by mitochondrial hyperfusion

“…In C. elegans, FZO-1 and EAT-3 are required for the fusion of the outer mitochondrial membrane and the inner mitochondrial membrane, respectively (7,(10)(11)(12)(13). To determine whether mitochondrial hyperfusion induced by mma-1(RNAi) is dependent on these GTPases, we performed RNAi experiments in animals carrying a null-mutation in the fzo-1 gene [fzo-1(tm1133)] or the eat-3 gene [eat-3(tm1107)].…”

“…For example, mammalian Drp1 or Caenorhabditis elegans DRP-1 are required for mitochondrial fission (6,7). Conversely, mammalian Mfn1/2 and Opa1 or C. elegans FZO-1 and EAT-3 are required for the fusion of the outer and inner mitochondrial membrane, respectively (8)(9)(10)(11)(12)(13).…”