論文 - 詳細
| RRC ID | 65251 |
|---|---|
| 著者 | Liu YJ, McIntyre RL, Janssens GE, Williams EG, Lan J, van Weeghel M, Schomakers B, van der Veen H, van der Wel NN, Yao P, Mair WB, Aebersold R, MacInnes AW, Houtkooper RH. |
| タイトル | Mitochondrial translation and dynamics synergistically extend lifespan in C. elegans through HLH-30. |
| ジャーナル | J Cell Biol |
| Abstract |
Mitochondrial form and function are closely interlinked in homeostasis and aging. Inhibiting mitochondrial translation is known to increase lifespan in C. elegans, and is accompanied by a fragmented mitochondrial network. However, whether this link between mitochondrial translation and morphology is causal in longevity remains uncharacterized. Here, we show in C. elegans that disrupting mitochondrial network homeostasis by blocking fission or fusion synergizes with reduced mitochondrial translation to prolong lifespan and stimulate stress response such as the mitochondrial unfolded protein response, UPRMT. Conversely, immobilizing the mitochondrial network through a simultaneous disruption of fission and fusion abrogates the lifespan increase induced by mitochondrial translation inhibition. Furthermore, we find that the synergistic effect of inhibiting both mitochondrial translation and dynamics on lifespan, despite stimulating UPRMT, does not require it. Instead, this lifespan-extending synergy is exclusively dependent on the lysosome biogenesis and autophagy transcription factor HLH-30/TFEB. Altogether, our study reveals the mechanistic crosstalk between mitochondrial translation, mitochondrial dynamics, and lysosomal signaling in regulating longevity. |
| 巻・号 | 219(6) |
| 公開日 | 2020-6-1 |
| DOI | 10.1083/jcb.201907067 |
| PII | 151623 |
| PMID | 32259199 |
| PMC | PMC7265311 |
| MeSH | Animals Autophagosomes / drug effects Autophagosomes / metabolism Autophagosomes / ultrastructure Basic Helix-Loop-Helix Transcription Factors / genetics Basic Helix-Loop-Helix Transcription Factors / metabolism* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Gene Ontology Longevity / genetics Longevity / physiology* Lysosomes / drug effects Lysosomes / metabolism Lysosomes / ultrastructure Microscopy, Electron, Transmission Mitochondria / genetics Mitochondria / metabolism* Mitochondrial Dynamics / drug effects* Protein Biosynthesis / drug effects* Protein Biosynthesis / physiology Proteomics RNA Interference Reproduction / physiology Signal Transduction / drug effects Signal Transduction / physiology Unfolded Protein Response / drug effects Unfolded Protein Response / genetics |
| 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 | 87 |
| 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 tm1133 tm1107 |