Hormetic heat shock and HSF-1 overexpression improve C. elegans survival and proteostasis by inducing autophagy.
The cellular recycling process of macroautophagy/autophagy is an essential homeostatic system induced by various stresses, but it remains unclear how autophagy contributes to organismal stress resistance. In a recent study, we report that a mild and physiologically beneficial ("hormetic") heat shock as well as overexpression of the heat-shock responsive transcription factor HSF-1 systemically increases autophagy in C. elegans. Accordingly, we found HSF-1- and heat stress-inducible autophagy to be required for C. elegans thermoresistance and longevity. Moreover, a hormetic heat shock or HSF-1 overexpression alleviated PolyQ protein aggregation in an autophagy-dependent manner. Collectively, we demonstrate a critical role for autophagy in C. elegans stress resistance and hormesis, and reveal a requirement for autophagy in HSF-1 regulated functions in the heat-shock response, proteostasis, and aging.
a Sanford Burnham Prebys Medical Discovery Institute, Development, Aging, and Regeneration Program , La Jolla , CA USA.
Caroline
C
Kumsta
a Sanford Burnham Prebys Medical Discovery Institute, Development, Aging, and Regeneration Program , La Jolla , CA USA.
Malene
M
Hansen
D000818:Animals; D001343:Autophagy; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D018869:Heat-Shock Response; D059165:Hormesis; D008954:Models, Biological; D000074702:Proteostasis; D013312:Stress, Physiological; D016019:Survival Analysis; D014157:Transcription Factors / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D014157:Transcription Factors; C474710:heat shock factor-1, C elegans
C. elegans; HLH-30; HSF-1; aging; autophagy; heat shock; hormesis; polyQ aggregation; proteostasis; stress resistance