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
リソース情報
線虫 tm1944 tm2369 tm2658