Cell Metabolism
Volume 12, Issue 3, 8 September 2010, Pages 260-272
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Article
Insulin-like Signaling Determines Survival during Stress via Posttranscriptional Mechanisms in C. elegans

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Summary

The insulin-like signaling (ILS) pathway regulates metabolism and is known to modulate adult life span in C. elegans. Altered stress responses and resistance to a wide range of stressors are also associated with changes in ILS and contribute to enhanced longevity. The transcription factors DAF-16 and HSF-1 are key effectors of the longevity phenotype. We demonstrate that increased intrinsic thermotolerance, due to lower ILS, is not dependent on stress-induced transcriptional responses but instead requires active protein translation. Translation profiling experiments reveal genes that are posttranscriptionally regulated in response to altered ILS during heat shock in a DAF-16-dependent manner. Furthermore, several novel proteins are specifically required for ILS effects on thermotolerance. We propose that lowered ILS results in metabolic and physiological changes. These DAF-16-induced changes precondition a translational response under acute stress to modulate survival.

Highlights

► In C. elegans, insulin-like signaling (ILS) activity modulates thermotolerance ► ILS increased thermotolerance does not require induced transcriptional responses ► Active translation, however, is crucial for ILS increased thermotolerance ► Translational profiling has identified specific genes required for resistance

HUMDISEASE
SIGNALING

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