Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. Signal., 13 January 2009
Vol. 2, Issue 53, p. ec12
[DOI: 10.1126/scisignal.253ec12]

EDITORS' CHOICE

Metabolism Surviving Hard Times

Elizabeth M. Adler

Science Signaling, AAAS, Washington, DC 20005, USA

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 {alpha}2 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]

Citation: E. M. Adler, Surviving Hard Times. Sci. Signal. 2, ec12 (2009).



To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882