| RRC ID |
51441
|
| 著者 |
Webster CM, Pino EC, Carr CE, Wu L, Zhou B, Cedillo L, Kacergis MC, Curran SP, Soukas AA.
|
| タイトル |
Genome-wide RNAi Screen for Fat Regulatory Genes in C. elegans Identifies a Proteostasis-AMPK Axis Critical for Starvation Survival.
|
| ジャーナル |
Cell Rep
|
| Abstract |
Organisms must execute metabolic defenses to survive nutrient deprivation. We performed a genome-wide RNAi screen in Caenorhabditis elegans to identify fat regulatory genes indispensable for starvation resistance. Here, we show that opposing proteostasis pathways are principal determinants of starvation survival. Reduced function of cytoplasmic aminoacyl tRNA synthetases (ARS genes) increases fat mass and extends starvation survival, whereas reduced proteasomal function reduces fat and starvation survival. These opposing pathways converge on AMP-activated protein kinase (AMPK) as the critical effector of starvation defenses. Extended starvation survival in ARS deficiency is dependent upon increased proteasome-mediated activation of AMPK. When the proteasome is inhibited, neither starvation nor ARS deficiency can fully activate AMPK, leading to greatly diminished starvation survival. Thus, activity of the proteasome and AMPK are mechanistically linked and highly correlated with starvation resistance. Conversely, aberrant activation of the proteostasis-AMPK axis during nutritional excess may have implications for obesity and cardiometabolic diseases.
|
| 巻・号 |
20(3)
|
| ページ |
627-640
|
| 公開日 |
2017-7-18
|
| DOI |
10.1016/j.celrep.2017.06.068
|
| PII |
S2211-1247(17)30899-9
|
| PMID |
28723566
|
| PMC |
PMC5578715
|
| MeSH |
AMP-Activated Protein Kinases / genetics
AMP-Activated Protein Kinases / metabolism*
Animals
Caenorhabditis elegans / genetics
Caenorhabditis elegans / metabolism*
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism*
Genome-Wide Association Study
Proteostasis / physiology*
|
| IF |
8.109
|
| 引用数 |
7
|
| リソース情報 |
| 線虫 |
tm1944 |
