論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 180 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm1108 |