RRC ID 59526
Author Lan J, Rollins JA, Zang X, Wu D, Zou L, Wang Z, Ye C, Wu Z, Kapahi P, Rogers AN, Chen D.
Title Translational Regulation of Non-autonomous Mitochondrial Stress Response Promotes Longevity.
Journal Cell Rep
Abstract Reduced mRNA translation delays aging, but the underlying mechanisms remain underexplored. Mutations in both DAF-2 (IGF-1 receptor) and RSKS-1 (ribosomal S6 kinase/S6K) cause synergistic lifespan extension in C. elegans. To understand the roles of translational regulation in this process, we performed polysomal profiling and identified translationally regulated ribosomal and cytochrome c (CYC-2.1) genes as key mediators of longevity. cyc-2.1 knockdown significantly extends lifespan by activating the intestinal mitochondrial unfolded protein response (UPRmt), mitochondrial fission, and AMP-activated kinase (AMPK). The germline serves as the key tissue for cyc-2.1 to regulate lifespan, and germline-specific cyc-2.1 knockdown non-autonomously activates intestinal UPRmt and AMPK. Furthermore, the RNA-binding protein GLD-1-mediated translational repression of cyc-2.1 in the germline is important for the non-autonomous activation of UPRmt and synergistic longevity of the daf-2 rsks-1 mutant. Altogether, these results illustrate a translationally regulated non-autonomous mitochondrial stress response mechanism in the modulation of lifespan by insulin-like signaling and S6K.
Volume 28(4)
Pages 1050-1062.e6
Published 2019-7-23
DOI 10.1016/j.celrep.2019.06.078
PII S2211-1247(19)30858-7
PMID 31340143
PMC PMC6684276
MeSH AMP-Activated Protein Kinases / metabolism Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Down-Regulation / genetics Enzyme Activation Genes, Helminth Genome Germ Cells / metabolism Longevity / physiology* Mitochondria / metabolism* Mitochondrial Dynamics Mutation / genetics Organ Specificity Protein Biosynthesis* Signal Transduction Stress, Physiological* Unfolded Protein Response
IF 7.815
Times Cited 5
C.elegans tm1108