RRC ID 45928
Author Bennett CF, Vander Wende H, Simko M, Klum S, Barfield S, Choi H, Pineda VV, Kaeberlein M.
Title Activation of the mitochondrial unfolded protein response does not predict longevity in Caenorhabditis elegans.
Journal Nat Commun
Abstract Recent studies have propagated the model that the mitochondrial unfolded protein response (UPR(mt)) is causal for lifespan extension from inhibition of the electron transport chain (ETC) in Caenorhabditis elegans. Here we report a genome-wide RNAi screen for negative regulators of the UPR(mt). Lifespan analysis of nineteen RNAi clones that induce the hsp-6p::gfp reporter demonstrate differential effects on longevity. Deletion of atfs-1, which is required for induction of the UPR(mt), fails to prevent lifespan extension from knockdown of two genes identified in our screen or following knockdown of the ETC gene cco-1. RNAi knockdown of atfs-1 also has no effect on lifespan extension caused by mutation of the ETC gene isp-1. Constitutive activation of the UPR(mt) by gain of function mutations in atfs-1 fails to extend lifespan. These observations identify several new factors that promote mitochondrial homoeostasis and demonstrate that the UPR(mt), as currently defined, is neither necessary nor sufficient for lifespan extension.
Volume 5
Pages 3483
Published 2014-3-24
DOI 10.1038/ncomms4483
PII ncomms4483
PMID 24662282
PMC PMC3984390
MeSH Animals Caenorhabditis elegans / metabolism Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Gene Knockdown Techniques Green Fluorescent Proteins Longevity / physiology* Mitochondria / metabolism* RNA Interference Real-Time Polymerase Chain Reaction Transcription Factors / genetics Unfolded Protein Response / physiology*
IF 12.121
Times Cited 86
C.elegans tm4525 tm425