Hormetic heat stress and HSF-1 induce autophagy to improve survival and proteostasis in C. elegans

Kumsta, Caroline; Chang, Jessica T.; Schmalz, Jessica; Hansen, Malene

doi:10.1038/ncomms14337

Cited by 209 publications

(215 citation statements)

References 70 publications

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“…In poikilotherms, autophagy has been found to help Caenorhabditis elegans survive heat stress (Kumsta et al . ), but a study on D. melanogaster showed a negative effect of autophagy caused by fasting on resisting cold stress (Le Bourg & Massou, ). The present study revealed that activation of autophagy due to fasting is an important mechanism of fish to resist cold stress.…”

Section: Discussionmentioning

confidence: 99%

Fasting enhances cold resistance in fish through stimulating lipid catabolism and autophagy

Wang

et al. 2019

The Journal of Physiology

100

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Key points In a cold environment, mammals increase their food intake while fish decrease or stop feeding. However, the physiological value of fasting during cold resistance in fish is currently unknown. Fasting for more than 48 h enhanced acute cold resistance in zebrafish, which correlated with lipid catabolism and cell damage attenuation. Lipid catabolism and autophagy were necessary for cold resistance in fish and the inhibition of mitochondrial fatty acid β‐oxidation or autophagy weakened the fasting‐induced cold resistance. Repression of mechanistic target of rapamycin (mTOR) signalling pathway by rapamycin largely mimicked the beneficial effects of fasting in promoting cold resistance, suggesting mTOR signalling may be involved in the fasting‐induced cold resistance in fish. Our study demonstrates that fasting may be a protective strategy for fish to survive under cold stress. Abstract In cold environments, most homeothermic animals increase their food intake to supply more energy to maintain body temperature, whereas most poikilothermic animals such as fishes decrease or even stop feeding under cold stress. However, the physiological value of fasting during cold resistance in poikilotherms has not been explained. Here, we show that moderate fasting largely enhanced cold resistance in fish. By using pharmacological (fenofibrate, mildronate, chloroquine and rapamycin) and nutritional approaches (fatty acids diets and amino acids diets) in wild‐type or specific gene knock‐out zebrafish models (carnitine palmitoyltransferase‐1b‐deficient strain, CPT1b−/−, or autophagy‐related protein 12‐deficient strain, ATG12−/−), we verified that fasting‐stimulated lipid catabolism and autophagy played essential roles in the improved cold resistance. Moreover, suppression of the mechanistic target of rapamycin (mTOR) pathway by using rapamycin mostly mimicked the beneficial effects of fasting in promoting cold resistance as either the physiological phenotype or transcriptomic pattern. However, these beneficial effects were largely reduced when the mTOR pathway was activated through high dietary leucine supplementation. We conclude that fasting helps fish to resist cold stress by modulating lipid catabolism and autophagy, which correlates with the mTOR signalling pathway. Therefore, fasting can act as a protective strategy of fish in resisting coldness.

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Section: Discussionmentioning

confidence: 99%

Fasting enhances cold resistance in fish through stimulating lipid catabolism and autophagy

Wang

et al. 2019

The Journal of Physiology

100

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“…RNAi experiments were performed as described in (31). The HSF-1 overexpression strain EQ87, hsf-1p::hsf-1::gfp + rol-6, was used for HSF-1 overexpression studies (32,33).…”

Section: Hsf-1 Rnai and Overexpressionmentioning

confidence: 99%

Remodeling of theC. elegansNon-coding RNA Transcriptome by Heat Shock

Schreiner¹,

Pagliuso²,

Garrigues³

et al. 2019

Preprint

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Elevated temperatures activate a Heat Shock Response (HSR) to protect cells from the pathological effects of protein mis-folding, cellular mis-organization, organelle dysfunction and altered membrane fluidity. This response includes activation of the conserved transcription factor Heat Shock Factor 1 (HSF-1), which binds Heat Shock Elements (HSEs) in the promoters of genes induced by heat shock (HS). The upregulation of protein-coding genes (PCGs), such as Heat Shock Proteins (HSPs) and cytoskeletal regulators, is critical for cellular survival during elevated temperatures. While the transcriptional response of PCGs to heat shock has been comprehensively analyzed in a variety of organisms, the effect of this stress on the expression of noncoding RNAs (ncRNAs) has not been systematically examined. Here we show that in Caenorhabditis elegans HS induces up-and down-regulation of specific ncRNAs from multiple classes, including miRNA, piRNA, lincRNA, pseudogene, and repeat elements. Moreover, some ncRNA genes appear to be direct targets of the HSR, as they contain HSF-1 bound HSEs in their promoters and their expression is regulated by this factor during HS. These results demonstrate that multiple ncRNA genes respond to HS, some as direct HSF-1 targets, providing new candidates that may contribute to organismal survival during this stress.

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“…Since modulation of autophagy has been found to be essential in many long-lived paradigms, we questioned whether ehbp-1-mediated lipophagy and ER remodeling was a critical contributor of lifespan extension in other long-lived models (Kumsta et al, 2017). Nematodes with mutations in the insulin receptor, daf-2, live significantly longer than wild type controls (Kenyon et al, 1993).…”

Section: A Lipophagy Complex Mediates Cerm Formation and Lipid Turnovmentioning

confidence: 99%

A non-canonical arm of UPR^ER mediates longevity through ER remodeling and lipophagy

Danièle

Higuchi‐Sanabria

Vignesh

et al. 2018

Preprint

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Longevity is dictated by a combination of environmental and genetic factors. One of the key mechanisms implicated in regulating lifespan extension is the ability to induce protein chaperones to promote protein homeostasis. However, it is unclear whether protein chaperones exclusively regulate longevity. Previous work has shown that activating the unfolded protein response of the endoplasmic reticulum (UPR ER ) in neurons can signal peripheral tissues to promote chaperone expression, thus enhancing organismal stress resistance and extending lifespan. Here, we find that this activation not only promotes chaperones, but facilitates a dramatic restructuring of ER morphology in intestinal cells. This restructuring, which includes depletion of lipid droplets, ER expansion, and ER tubulation, depends of lipophagy. Surprisingly, we find that lipophagy is required for lifespan extension and is completely independent of chaperone function. Therefore, UPR induction in neurons triggers two distinct programs in the periphery: the canonical arm through protein chaperones, and a non-canonical mechanism through lipid depletion. In summary, our study identifies lipophagy as an integral component of UPR ER -induced longevity. MAINLife presents a myriad of challenges, stressors, and environmental shifts to which cells must adapt in order to survive and thrive. The homeostatic regulation of protein folding (proteostasis), which is monitored in specific subcellular compartments (the endoplasmic reticulum (ER), mitochondria, cytosol) is an integral player in stress resistance and longevity. The ER, in particular, is a central regulator of stress monitoring since it controls (1) nearly a third of the cell's proteins, (2) provides an internal medium and transponder for lipid homeostasis and cell signaling, and (3) communicates directly with all other organelles to maintain cellular secretion.

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Hormetic heat stress and HSF-1 induce autophagy to improve survival and proteostasis in C. elegans

Cited by 209 publications

References 70 publications

Fasting enhances cold resistance in fish through stimulating lipid catabolism and autophagy

Fasting enhances cold resistance in fish through stimulating lipid catabolism and autophagy

Remodeling of theC. elegansNon-coding RNA Transcriptome by Heat Shock

A non-canonical arm of UPR^ER mediates longevity through ER remodeling and lipophagy

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Hormetic heat stress and HSF-1 induce autophagy to improve survival and proteostasis in C. elegans

Cited by 209 publications

References 70 publications

Fasting enhances cold resistance in fish through stimulating lipid catabolism and autophagy

Fasting enhances cold resistance in fish through stimulating lipid catabolism and autophagy

Remodeling of theC. elegansNon-coding RNA Transcriptome by Heat Shock

A non-canonical arm of UPRER mediates longevity through ER remodeling and lipophagy

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A non-canonical arm of UPR^ER mediates longevity through ER remodeling and lipophagy