RRC ID 59506
著者 Herholz M, Cepeda E, Baumann L, Kukat A, Hermeling J, Maciej S, Szczepanowska K, Pavlenko V, Frommolt P, Trifunovic A.
タイトル KLF-1 orchestrates a xenobiotic detoxification program essential for longevity of mitochondrial mutants.
ジャーナル Nat Commun
Abstract Most manipulations that extend lifespan also increase resistance to various stress factors and environmental cues in a range of animals from yeast to mammals. However, the underlying molecular mechanisms regulating stress resistance during aging are still largely unknown. Here we identify Krüppel-like factor 1 (KLF-1) as a mediator of a cytoprotective response that dictates longevity induced by reduced mitochondrial function. A redox-regulated KLF-1 activation and transfer to the nucleus coincides with the peak of somatic mitochondrial biogenesis that occurs around a transition from larval stage L3 to D1. We further show that KLF-1 activates genes involved in the xenobiotic detoxification programme and identified cytochrome P450 oxidases, the KLF-1 main effectors, as longevity-assurance factors of mitochondrial mutants. Collectively, these findings underline the importance of the xenobiotic detoxification in the mitohormetic, longevity assurance pathway and identify KLF-1 as a central factor in orchestrating this response.
巻・号 10(1)
ページ 3323
公開日 2019-7-25
DOI 10.1038/s41467-019-11275-w
PII 10.1038/s41467-019-11275-w
PMID 31346165
PMC PMC6658563
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Nucleus / genetics Cell Nucleus / metabolism Female Inactivation, Metabolic Kruppel-Like Transcription Factors / genetics Kruppel-Like Transcription Factors / metabolism* Longevity Male Mitochondria / genetics* Mitochondria / metabolism Xenobiotics / metabolism*
IF 11.878
引用数 0
リソース情報
線虫 tm1110