Herholz, Marija, Cepeda, Estela, Baumann, Linda, Kukat, Alexandra, Hermeling, Johannes, Maciej, Sarah, Szczepanowska, Karolina, Pavlenko, Victor, Frommolt, Peter ORCID: 0000-0002-1966-8014 and Trifunovic, Aleksandra ORCID: 0000-0002-5472-3517 (2019). KLF-1 orchestrates a xenobiotic detoxification program essential for longevity of mitochondrial mutants. Nat. Commun., 10. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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 Kruppel-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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Herholz, MarijaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cepeda, EstelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baumann, LindaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kukat, AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hermeling, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maciej, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Szczepanowska, KarolinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pavlenko, VictorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frommolt, PeterUNSPECIFIEDorcid.org/0000-0002-1966-8014UNSPECIFIED
Trifunovic, AleksandraUNSPECIFIEDorcid.org/0000-0002-5472-3517UNSPECIFIED
URN: urn:nbn:de:hbz:38-134701
DOI: 10.1038/s41467-019-11275-w
Journal or Publication Title: Nat. Commun.
Volume: 10
Date: 2019
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
LIFE-SPAN; SUPEROXIDE-PRODUCTION; ELECTRON-TRANSPORT; FUNCTIONAL-ANALYSIS; OXIDATIVE STRESS; C-ELEGANS; EXPRESSION; DNA; CYTOCHROME-P450; METABOLISMMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13470

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