RRC ID |
45928
|
著者 |
Bennett CF, Vander Wende H, Simko M, Klum S, Barfield S, Choi H, Pineda VV, Kaeberlein M.
|
タイトル |
Activation of the mitochondrial unfolded protein response does not predict longevity in Caenorhabditis elegans.
|
ジャーナル |
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.
|
巻・号 |
5
|
ページ |
3483
|
公開日 |
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
|
引用数 |
86
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
線虫 |
tm4525
tm425 |