RRC ID 46268
著者 Bess AS, Crocker TL, Ryde IT, Meyer JN.
タイトル Mitochondrial dynamics and autophagy aid in removal of persistent mitochondrial DNA damage in Caenorhabditis elegans.
ジャーナル Nucleic Acids Res
Abstract Mitochondria lack the ability to repair certain helix-distorting lesions that are induced at high levels in mitochondrial DNA (mtDNA) by important environmental genotoxins and endogenous metabolites. These lesions are irreparable and persistent in the short term, but their long-term fate is unknown. We report that removal of such mtDNA damage is detectable by 48 h in Caenorhabditis elegans, and requires mitochondrial fusion, fission and autophagy, providing genetic evidence for a novel mtDNA damage removal pathway. Furthermore, mutations in genes involved in these processes as well as pharmacological inhibition of autophagy exacerbated mtDNA damage-mediated larval arrest, illustrating the in vivo relevance of removal of persistent mtDNA damage. Mutations in genes in these pathways exist in the human population, demonstrating the potential for important gene-environment interactions affecting mitochondrial health after genotoxin exposure.
巻・号 40(16)
ページ 7916-31
公開日 2012-9-1
DOI 10.1093/nar/gks532
PII gks532
PMID 22718972
PMC PMC3439916
MeSH Animals Autophagy* Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans / radiation effects DNA Damage* DNA Replication DNA, Mitochondrial / biosynthesis DNA, Mitochondrial / metabolism* DNA, Mitochondrial / radiation effects Larva / genetics Larva / radiation effects Mitochondria / ultrastructure Mitochondrial Dynamics* Ultraviolet Rays / adverse effects
IF 11.502
引用数 56
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
線虫 tm1133 tm1108 tm1779