KLF-1 orchestrates a xenobiotic detoxification program essential for longevity of mitochondrial mutants

Marija Herholz, Estela Cepeda, Linda Baumann, Alexandra Kukat, Johannes Hermeling, Sarah Maciej, Karolina Szczepanowska, Victor Pavlenko, Peter Frommolt and Aleksandra Trifunovic ()
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Marija Herholz: University of Cologne
Estela Cepeda: University of Cologne
Linda Baumann: University of Cologne
Alexandra Kukat: University of Cologne
Johannes Hermeling: University of Cologne
Sarah Maciej: University of Cologne
Karolina Szczepanowska: University of Cologne
Victor Pavlenko: University of Cologne
Peter Frommolt: University of Cologne
Aleksandra Trifunovic: University of Cologne

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11275-w

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