the homeobox protein ceh-23 mediates prolonged longevity in response to impaired mitochondrial electron transport chain in c. elegans同源框蛋白ceh-23介导延长寿命,以应对受损在秀丽隐杆线虫线粒体电子传递链.pdfVIP

The Homeobox Protein CEH-23 Mediates Prolonged Longevity in Response to Impaired Mitochondrial Electron Transport Chain in C. elegans ¤ Ludivine Walter , Aiswarya Baruah, Hsin-Wen Chang, Heather Mae Pace, Siu Sylvia Lee* Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America 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. Citation: Walter L, Baruah A, Chang H-W, Pace HM, Lee SS (2011) The Homeobox Protein CEH-23 Mediates Prolonged Longevity in Response to Impaired Mitochondrial Electron Transport Chain in C. elegans. PLoS Biol 9(6): e1001084. doi:10.1371/journal.pbio.1001084 Academic Editor: Andy Dillin, The Salk Institute for Biological Studies, United States of America Received November 8, 2010; A