Editors' ChoiceMetabolism

Surviving Hard Times

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Sci. Signal.  13 Jan 2009:
Vol. 2, Issue 53, pp. ec12
DOI: 10.1126/scisignal.253ec12

Adverse conditions promote the entry of Caenorhabditis elegans larvae into dauer, a developmentally arrested state in which they do not feed, are resistant to stress, and survive for extended periods of time. Reduced insulin-like signaling (ILS) elicits dauer, and life-span extension in dauer larvae with mutationally suppressed ILS depends on signaling through the LKB1-AMPK (AMP-activated protein kinase) pathway. Thus, larvae with mutant aak-2 (encoding the C. elegans AMPK α2 catalytic subunit) do not show long-term survival. Narbonne and Roy found that conditional expression of aak-2 in hypodermal and excretory cells partially rescued dauer life span in aak-2 mutant larvae with impaired ILS, whereas its expression in other cells did not. C. elegans hypodermis acts as an adipose-like tissue, storing fat in preparation for dauer, and aak-2 mutant dauer larvae rapidly depleted lipid stores, whereas larvae with ILS defects alone did not. Moreover, oxygen consumption was greater in aak-2 mutant dauer larvae compared with controls. The rapid triglyceride hydrolysis found in aak-2 dauer mutants was blocked by RNAi-mediated knockdown of adipose triglyceride lipase (ATGL-1), a manipulation that also substantially rescued life span. AMPK phosphorylated ATGL-1 on Ser303, and ubiquitous expression of an ATGL-1 Ser303 → Ala303 variant enhanced lipid loss relative to that with expression of wild-type ATGL-1. Dauer larvae with compromised ILS are resistant to hypertonic stress; although aak-2 mutation did not initially affect this resistance, it was lost in older aak-2 mutant dauers. Moreover, addition of 20 or 50 mM NaCl to culture media reduced the life span of aak-2 mutant dauer without affecting that of controls. Thus, the authors propose that LKB1-AMPK signaling enhances survival in dauer by slowing the depletion of lipid stores and thereby maintaining osmoregulation.

P. Narbonne, R. Roy, Caenorhabditis elegans dauers need LKB1/AMPK to ration lipid reserves and ensure long-term survival. Nature 457, 210–214 (2009). [PubMed]