biostudies-literatureUnknown58Hermeling JCDeutsche ForschungsgemeinschaftAlternations of redox metabolism have been associated with the extension of lifespan in roundworm Caenorhabditis elegans, caused by moderate mitochondrial dysfunction, although the underlying signalling cascades are largely unknown. Previously, we identified transcriptional factor Krüppel-like factor-1 (KLF-1) as the main regulator of cytoprotective longevity-assurance pathways in the C. elegans long-lived mitochondrial mutants. Here, we show that KLF-1 translocation to the nucleus and the activation of the signalling cascade is dependent on the mitochondria-derived hydrogen peroxide (H₂O₂) produced during late developmental phases where aerobic respiration and somatic mitochondrial biogenesis peak. We further show that mitochondrial-inducible superoxide dismutase-3 (Redox biology102533https://www.ebi.ac.uk/biostudies/studies/S-EPMC9709155biostudies-literatureMitochondria-originated redox signalling regulates KLF-1 to promote longevity in Caenorhabditis elegans.PMC9709155Trifunovic ARiemer JHerholz MCores ECHoppe THermeling JCBaumann LZecic AfalseMitochondria-originated redox signalling regulates KLF-1 to promote longevity in Caenorhabditis elegans.Alternations of redox metabolism have been associated with the extension of lifespan in roundworm Caenorhabditis elegans, caused by moderate mitochondrial dysfunction, although the underlying signalling cascades are largely unknown. Previously, we identified transcriptional factor Krüppel-like factor-1 (KLF-1) as the main regulator of cytoprotective longevity-assurance pathways in the C. elegans long-lived mitochondrial mutants. Here, we show that KLF-1 translocation to the nucleus and the activation of the signalling cascade is dependent on the mitochondria-derived hydrogen peroxide (H₂O₂) produced during late developmental phases where aerobic respiration and somatic mitochondrial biogenesis peak. We further show that mitochondrial-inducible superoxide dismutase-3 (2022-01-01T00:00:00Z2022 Dec2025-04-05T11:39:37.703Z2025-04-05T11:39:37.703ZS-EPMC97091553644239410.1016/j.redox.2022.102533