The homeobox protein CEH-23 mediates prolonged longevity in response to impaired mitochondrial electron transport chain in C. elegans.

Authors: Walter, Ludivine; Baruah, Aiswarya; Chang, Hsin-Wen; Pace, Heather Mae; Lee, Siu Sylvia

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.

Keywords: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins/genetics/*physiology; Drug Resistance; Electron Transport/genetics; Electron Transport Complex III/genetics; Homeodomain Proteins/*physiology; Longevity/drug effects/*genetics; Mitochondria/genetics/*physiology; Neurons/metabolism; Paraquat/pharmacology; RNA Interference; Transcription Factors/*physiology
Journal: PLoS Biol
Volume: 9
Issue: 6
Pages: e1001084
Date: June 30, 2011
PMID: 21713031


Citation:

Walter, Ludivine, Baruah, Aiswarya, Chang, Hsin-Wen, Pace, Heather Mae, Lee, Siu Sylvia (2011) The homeobox protein CEH-23 mediates prolonged longevity in response to impaired mitochondrial electron transport chain in C. elegans. PLoS Biol 9: e1001084.


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