KLF-1 orchestrates a xenobiotic detoxification program essential for longevity of mitochondrial mutants
In: Nature Communications, Jg. 10 (2019), Heft 1, S. 1-15
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Zugriff:
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.
Cytochrome P450 oxidases (CYPs) are enzymes that participate in the xenobiotic detoxification and their expression is enhanced in long-lived model organisms. Here the authors show that KLF-1 promotes cyp expression and ensures lifespan extension in C. elegans mitomutants by activating mitohormesis.
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KLF-1 orchestrates a xenobiotic detoxification program essential for longevity of mitochondrial mutants
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Autor/in / Beteiligte Person: | Baumann, Linda ; Herholz, Marija ; Trifunovic, Aleksandra ; Kukat, Alexandra ; Cepeda, Estela ; Szczepanowska, Karolina ; Pavlenko, Victor ; Frommolt, Peter ; Hermeling, Johannes ; Maciej, Sarah |
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Zeitschrift: | Nature Communications, Jg. 10 (2019), Heft 1, S. 1-15 |
Veröffentlichung: | Nature Publishing Group, 2019 |
Medientyp: | unknown |
ISSN: | 2041-1723 (print) |
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