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Fatty acids are essential components of all living organisms and the fatty acid metabolism mechanisms are conserved across species. Fatty acids are important for membrane biogenesis, energy storage and they serve as signaling molecules and modulate growth and development. Caenorhabditis elegans (C. elegans) does not have adipocytes dedicated to fat storage like in mammals, hence they store fats as triglycerides (TAGs) in lipid droplets and yolk. In C. elegans, the intestine is the major organ where food absorption, incorporation of nutrients into metabolic pathways, fat storage and utilization take place. Fatty acid synthesis, elongation, and desaturation, such as mitochondrial and peroxisomal ß-oxidation of fatty acids, are conserved in C. elegans. Previously, we identified Krüppel-like factor 1 (KLF-1) as a major regulator of the longevity assurance caused by mitochondrial dysfunction in C. elegans. Now, we show that KLF-1 negatively regulates neutral lipid levels in C. elegans mitochondrial isp-1(qm150);ctb-1(qm189) mutants, a defect that can be fully corrected upon klf-1 knockdown. The role of KLF-1 in the regulation of genes involved in lipid metabolism and storage in isp-1;ctb-1 mutants is further emphasized by our microarray study. Moreover, we identified ACS-1, a peroxisomal acyl-CoA synthetase, to be essential for the longevity of mitochondrial isp-1;ctb-1 mutants. We also showed that PRX-5, a putative peroxisomal membrane protein, involved in protein import, has a similar role in suppression of increased lifespan in isp-1;ctb-1 worms. We further showed that both, ACS-1 and PRX-5 are important to sustain respiration in isp-1;ctb-1 mutants. Therefore, our data highlight the crosstalk between mitochondria and peroxisomes, especially lipid metabolism and shared fatty acid oxidation, as central to the response beneficial for organismal survival. Furthermore, we showed that loss of ACS-1 in isp-1;ctb-1 mutant induces massive lipid peroxidation and can trigger KL

Fatty acids are essential components of all living organisms and the fatty acid metabolism mechanisms are conserved across species. Fatty acids are important for membrane biogenesis, energy storage and they serve as signaling molecules and modulate growth and development. Caenorhabditis elegans (C. elegans) does not have adipocytes dedicated to fat storage like in mammals, hence they store fats as triglycerides (TAGs) in lipid droplets and yolk. In C. elegans, the intestine is the major organ where food absorption, incorporation of nutrients into metabolic pathways, fat storage and utilization take place. Fatty acid synthesis, elongation, and desaturation, such as mitochondrial and peroxisomal ß-oxidation of fatty acids, are conserved in C. elegans. Previously, we identified Krüppel-like factor 1 (KLF-1) as a major regulator of the longevity assurance caused by mitochondrial dysfunction in C. elegans. Now, we show that KLF-1 negatively regulates neutral lipid levels in C. elegans mitochondrial isp-1(qm150);ctb-1(qm189) mutants, a defect that can be fully corrected upon klf-1 knockdown. The role of KLF-1 in the regulation of genes involved in lipid metabolism and storage in isp-1;ctb-1 mutants is further emphasized by our microarray study. Moreover, we identified ACS-1, a peroxisomal acyl-CoA synthetase, to be essential for the longevity of mitochondrial isp-1;ctb-1 mutants. We also showed that PRX-5, a putative peroxisomal membrane protein, involved in protein import, has a similar role in suppression of increased lifespan in isp-1;ctb-1 worms. We further showed that both, ACS-1 and PRX-5 are important to sustain respiration in isp-1;ctb-1 mutants. Therefore, our data highlight the crosstalk between mitochondria and peroxisomes, especially lipid metabolism and shared fatty acid oxidation, as central to the response beneficial for organismal survival. Furthermore, we showed that loss of ACS-1 in isp-1;ctb-1 mutant induces massive lipid peroxidation and can trigger KL

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.

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.