論文 - 詳細
| RRC ID | 59639 |
|---|---|
| 著者 | Zhou B, Kreuzer J, Kumsta C, Wu L, Kamer KJ, Cedillo L, Zhang Y, Li S, Kacergis MC, Webster CM, Fejes-Toth G, Naray-Fejes-Toth A, Das S, Hansen M, Haas W, Soukas AA. |
| タイトル | Mitochondrial Permeability Uncouples Elevated Autophagy and Lifespan Extension. |
| ジャーナル | Cell |
| Abstract |
Autophagy is required in diverse paradigms of lifespan extension, leading to the prevailing notion that autophagy is beneficial for longevity. However, why autophagy is harmful in certain contexts remains unexplained. Here, we show that mitochondrial permeability defines the impact of autophagy on aging. Elevated autophagy unexpectedly shortens lifespan in C. elegans lacking serum/glucocorticoid regulated kinase-1 (sgk-1) because of increased mitochondrial permeability. In sgk-1 mutants, reducing levels of autophagy or mitochondrial permeability transition pore (mPTP) opening restores normal lifespan. Remarkably, low mitochondrial permeability is required across all paradigms examined of autophagy-dependent lifespan extension. Genetically induced mPTP opening blocks autophagy-dependent lifespan extension resulting from caloric restriction or loss of germline stem cells. Mitochondrial permeability similarly transforms autophagy into a destructive force in mammals, as liver-specific Sgk knockout mice demonstrate marked enhancement of hepatocyte autophagy, mPTP opening, and death with ischemia/reperfusion injury. Targeting mitochondrial permeability may maximize benefits of autophagy in aging. |
| 巻・号 | 177(2) |
| ページ | 299-314.e16 |
| 公開日 | 2019-4-4 |
| DOI | 10.1016/j.cell.2019.02.013 |
| PII | S0092-8674(19)30162-X |
| PMID | 30929899 |
| PMC | PMC6610881 |
| MeSH | Aging / metabolism* Animals Autophagy / physiology Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Caenorhabditis elegans Proteins / physiology Caloric Restriction HEK293 Cells Humans Longevity / physiology Male Mice Mice, Knockout Mitochondria Mitochondrial Membrane Transport Proteins / metabolism Mitochondrial Membrane Transport Proteins / physiology* Mitochondrial Membranes / physiology* Mitochondrial Permeability Transition Pore Permeability Primary Cell Culture Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism Protein Serine-Threonine Kinases / physiology Reperfusion Injury / metabolism Signal Transduction |
| IF | 36.216 |
| 引用数 | 19 |
| 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 | 174 |
| 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 | tm4525 |