論文 - 詳細
| RRC ID | 6415 |
|---|---|
| 著者 | Narbonne P, Roy R. |
| タイトル | Caenorhabditis elegans dauers need LKB1/AMPK to ration lipid reserves and ensure long-term survival. |
| ジャーナル | Nature |
| Abstract |
Many organisms can enter a dormant state or diapause to survive harsh environmental conditions for extended durations. When Caenorhabditis elegans larvae enter dauer they arrest feeding but remain active and motile, yet become stress-resistant, extremely long-lived and non-ageing. Entry into dauer is associated with a reduction in insulin-like signalling, the accumulation of nutritive resources and a concomitant global change in metabolism, yet the precise molecular and physiological processes that enable long-term survival in the absence of caloric intake remain largely unknown. We show here that C. elegans larvae that lack LKB1/AMPK (AMP-activated protein kinase) signalling enter dauer normally, but then rapidly consume their stored energy and prematurely expire following vital organ failure. We found that this signalling pathway acts in adipose-like tissues to downregulate triglyceride hydrolysis so that these lipid reserves are rationed to last the entire duration of the arrest. Indeed, the downregulation of adipose triglyceride lipase (ATGL-1) activity suppresses both the rapid depletion of stored lipids and reduced life span of AMPK mutant dauers, while AMPK directly phosphorylates ATGL-1. Finally, we show that the slow release of energy during dauer is critical for appropriate long-term osmoregulation, which fails as triglyceride resources become depleted. These mechanisms may be essential for survival through diapause, hibernation, or long-term fasting in diverse organisms and may also underlie AMPK-dependent life span extension. |
| 巻・号 | 457(7226) |
| ページ | 210-4 |
| 公開日 | 2009-1-8 |
| DOI | 10.1038/nature07536 |
| PII | nature07536 |
| PMID | 19052547 |
| MeSH | AMP-Activated Protein Kinases / chemistry AMP-Activated Protein Kinases / deficiency AMP-Activated Protein Kinases / genetics AMP-Activated Protein Kinases / metabolism* Adaptation, Physiological / physiology* Animals Caenorhabditis elegans / growth & development* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / antagonists & inhibitors Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Fasting / physiology Larva / metabolism Larva / physiology Life Cycle Stages / physiology* Lipase / antagonists & inhibitors Lipase / metabolism Lipid Metabolism* Longevity / genetics Longevity / physiology Phosphorylation Protein Serine-Threonine Kinases / deficiency Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism* Rats Signal Transduction Subcutaneous Tissue / metabolism Survival Analysis Time Factors Triglycerides / metabolism Water-Electrolyte Balance / genetics |
| IF | 42.779 |
| 引用数 | 202 |
| WOS 分野 | CELL BIOLOGY |
| 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 | F1000Research |
| 各媒体での言及数の合計 | 2 |
| 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 | tm1944 tm2369 tm2658 |