title: The homeobox protein CEH-23 mediates prolonged longevity in response to impaired mitochondrial electron transport chain in C. elegans.
abstract: Recent findings indicate that perturbations of the mitochondrial electron transport chain (METC) can cause extended longevity in evolutionarily diverse organisms. To uncover the molecular basis of how altered METC increases lifespan in C. elegans, we performed an RNAi screen and revealed that three predicted transcription factors are specifically required for the extended longevity of mitochondrial mutants. In particular, we demonstrated that the nuclear homeobox protein CEH-23 uniquely mediates the longevity but not the slow development, reduced brood size, or resistance to oxidative stress associated with mitochondrial mutations. Furthermore, we showed that ceh-23 expression levels are responsive to altered METC, and enforced overexpression of ceh-23 is sufficient to extend lifespan in wild-type background. Our data point to mitochondria-to-nucleus communications to be key for longevity determination and highlight CEH-23 as a novel longevity factor capable of responding to mitochondrial perturbations. These findings provide a new paradigm for how mitochondria impact aging and age-dependent diseases.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America.
authors.forename: Ludivine
authors.initials: L
authors.lastname: Walter
authors.forename: Aiswarya
authors.initials: A
authors.lastname: Baruah
authors.forename: Hsin-Wen
authors.initials: HW
authors.lastname: Chang
authors.forename: Heather Mae
authors.initials: HM
authors.lastname: Pace
authors.forename: Siu Sylvia
authors.initials: SS
authors.lastname: Lee
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D004351:Drug Resistance; D004579:Electron Transport / Q000235:genetics; D014450:Electron Transport Complex III / Q000235:genetics; D018398:Homeodomain Proteins / Q000502:physiology*; D008136:Longevity / Q000187:drug effects / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D010269:Paraquat / Q000494:pharmacology; D034622:RNA Interference; D014157:Transcription Factors / Q000502:physiology*
chemical_list: C561875:CEH-23 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; C443102:Isp-1 protein, Caenorhabditis elegans; D014450:Electron Transport Complex III; D010269:Paraquat