論文 - 詳細
| RRC ID | 53508 |
|---|---|
| 著者 | Xie M, Roy R. |
| タイトル | AMP-Activated Kinase Regulates Lipid Droplet Localization and Stability of Adipose Triglyceride Lipase in C. elegans Dauer Larvae. |
| ジャーナル | PLoS One |
| Abstract |
Animals have developed diverse mechanisms to adapt to their changing environment. Like many organisms the free-living nematode C. elegans can alternate between a reproductive mode or a diapause-like "dauer" stage during larval development to circumvent harsh environmental conditions. The master metabolic regulator AMP-activated protein kinase (AMPK) is critical for survival during the dauer stage, where it phosphorylates adipose triglyceride lipase (ATGL-1) at multiple sites to block lipid hydrolysis and ultimately protect the cellular triglyceride-based energy depot from rapid depletion. However, how the AMPK-mediated phosphorylation affects the function of ATGL-1 has not been characterised at the molecular level. Here we show that AMPK phosphorylation leads to the generation of 14-3-3 binding sites on ATGL-1, which are recognized by the C. elegans 14-3-3 protein orthologue PAR-5. Physical interaction of ATGL-1 with PAR-5 results in sequestration of ATGL-1 away from the lipid droplets and eventual proteasome-mediated degradation. In addition, we also show that the major AMPK phosphorylation site on ATGL-1, Ser 303, is required for both modification of its lipid droplet localization and its degradation. Our data provide mechanistic insight as to how AMPK functions to enhance survival through its ability to protect the accumulated triglyceride deposits from rapid hydrolysis to preserve the energy stores during periods of extended environmental duress. |
| 巻・号 | 10(6) |
| ページ | e0130480 |
| 公開日 | 2015-1-1 |
| DOI | 10.1371/journal.pone.0130480 |
| PII | PONE-D-15-13542 |
| PMID | 26098762 |
| PMC | PMC4476745 |
| MeSH | 14-3-3 Proteins / metabolism AMP-Activated Protein Kinases / metabolism* Animals Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Larva / metabolism* Lipase / metabolism* Lipid Droplets / metabolism* Lipid Metabolism / physiology Phosphorylation / physiology |
| IF | 2.74 |
| 引用数 | 13 |
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| 最多言及媒体 | X(Twitter) |
| 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 |
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