| RRC ID |
59526
|
| 著者 |
Lan J, Rollins JA, Zang X, Wu D, Zou L, Wang Z, Ye C, Wu Z, Kapahi P, Rogers AN, Chen D.
|
| タイトル |
Translational Regulation of Non-autonomous Mitochondrial Stress Response Promotes Longevity.
|
| ジャーナル |
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.
|
| 巻・号 |
28(4)
|
| ページ |
1050-1062.e6
|
| 公開日 |
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
|
| 引用数 |
5
|
| リソース情報 |
| 線虫 |
tm1108 |
