論文 - 詳細
| RRC ID | 59441 |
|---|---|
| 著者 | Aspernig H, Heimbucher T, Qi W, Gangurde D, Curic S, Yan Y, Donner von Gromoff E, Baumeister R, Thien A. |
| タイトル | Mitochondrial Perturbations Couple mTORC2 to Autophagy in C. elegans. |
| ジャーナル | Cell Rep |
| Abstract |
Autophagy is stimulated by stress conditions and needs to be precisely tuned to ensure cellular homeostasis and organismal development and health. The kinase mechanistic target of rapamycin (mTOR) forms the enzymatic core of the highly conserved mTOR complexes mTORC1 and mTORC2. mTORC1 is a key inhibitor of autophagy, yet the function of mTORC2 in autophagy is controversial. We here show that inactivation of mTORC2 and its direct target serum- and glucocorticoid-inducible kinase 1 (SGK-1) potently induces autophagy and the autophagic degradation of mitochondria in C. elegans. Enhanced autophagy in mTORC2- or SGK-1-deficient animals contributes to their developmental and reproductive defects and is independent of the canonical SGK-1 effector DAF-16/FOXO. Importantly, we find that inactivation of mTORC2-SGK-1 signaling impairs mitochondrial homeostasis and triggers an increased release of mitochondria-derived reactive oxygen species (mtROS) to induce autophagy. Thus, mitochondrial stress couples reduced mTORC2 activity to enhanced autophagic turnover. |
| 巻・号 | 29(6) |
| ページ | 1399-1409.e5 |
| 公開日 | 2019-11-5 |
| DOI | 10.1016/j.celrep.2019.09.072 |
| PII | S2211-1247(19)31269-0 |
| PMID | 31693882 |
| MeSH | Animals Caenorhabditis elegans / embryology Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Forkhead Transcription Factors / genetics Forkhead Transcription Factors / metabolism Mechanistic Target of Rapamycin Complex 2 / genetics Mechanistic Target of Rapamycin Complex 2 / metabolism* Mitochondria / metabolism* Mitophagy / genetics* Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism RNA Interference Rapamycin-Insensitive Companion of mTOR Protein / genetics Rapamycin-Insensitive Companion of mTOR Protein / metabolism Reactive Oxygen Species / metabolism Signal Transduction / genetics |
| IF | 7.815 |
| 引用数 | 5 |
| リソース情報 | |
| 線虫 | tm376 |