title: Hormetic heat stress and HSF-1 induce autophagy to improve survival and proteostasis in C. elegans.
abstract: Stress-response pathways have evolved to maintain cellular homeostasis and to ensure the survival of organisms under changing environmental conditions. Whereas severe stress is detrimental, mild stress can be beneficial for health and survival, known as hormesis. Although the universally conserved heat-shock response regulated by transcription factor HSF-1 has been implicated as an effector mechanism, the role and possible interplay with other cellular processes, such as autophagy, remains poorly understood. Here we show that autophagy is induced in multiple tissues of Caenorhabditis elegans following hormetic heat stress or HSF-1 overexpression. Autophagy-related genes are required for the thermoresistance and longevity of animals exposed to hormetic heat shock or HSF-1 overexpression. Hormetic heat shock also reduces the progressive accumulation of PolyQ aggregates in an autophagy-dependent manner. These findings demonstrate that autophagy contributes to stress resistance and hormesis, and reveal a requirement for autophagy in HSF-1-regulated functions in the heat-shock response, proteostasis and ageing.
authors.affiliation: Development, Aging, and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Kumsta
authors.affiliation: Development, Aging, and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Jessica T
authors.initials: JT
authors.lastname: Chang
authors.affiliation: Development, Aging, and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Schmalz
authors.affiliation: Development, Aging, and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Malene
authors.initials: M
authors.lastname: Hansen
mesh_terms: D000818:Animals; D001343:Autophagy; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018869:Heat-Shock Response; D059165:Hormesis; D010455:Peptides / Q000378:metabolism; D066329:Protein Aggregates; D000074702:Proteostasis; D016019:Survival Analysis; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D010455:Peptides; D066329:Protein Aggregates; D014157:Transcription Factors; C474710:heat shock factor-1, C elegans; D049452:Green Fluorescent Proteins; C097188:polyglutamine