RRC ID |
59506
|
Author |
Herholz M, Cepeda E, Baumann L, Kukat A, Hermeling J, Maciej S, Szczepanowska K, Pavlenko V, Frommolt P, Trifunovic A.
|
Title |
KLF-1 orchestrates a xenobiotic detoxification program essential for longevity of mitochondrial mutants.
|
Journal |
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.
|
Volume |
10(1)
|
Pages |
3323
|
Published |
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
|
Times Cited |
0
|
Resource |
C.elegans |
tm1110 |