HSF1 and Its Role in Huntington’s Disease Pathology

Kim, Hyuck; Gómez-Pastor, Rocío

doi:10.1007/5584_2022_742

Cited by 3 publications

(2 citation statements)

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“…We note that an analogous lipogenic role was described for mammalian HSF1 through the repression of the AMP-activated protein kinase AMPK 89 , illustrating a functional conservation of the crosstalk between HSF1 and lipid metabolism. HSF1 activity also exhibits age-dependent decline in mammals [90][91][92] . Whether this and/or analogous HSF1-dependent mechanisms modulate mammalian aging and obesity remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

An intestinal Sir2-HSF1-ATGL1 pathway regulates lipolysis inC. elegans

Somogyvári,

Khatatneh,

Hajdú

et al. 2024

Preprint

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Proteostasis maintenance and lipid metabolism are critical for survival and promote longevity, however, their coordination is largely unclear. Here we show that the heat shock factor HSF-1 and the proteostasis state regulates lipolysis in C. elegans. We find that in response to starvation, the sirtuin 1 ortholog SIR-2.1 activates lipolysis by upregulation of the adipose triglyceride lipase ATGL-1. In feeding worms, intestinal HSF-1 represses ATGL-1 expression and lipolysis via the microRNA system. In starving worms, SIR-2.1 suspends a miR-53-mediated suppression of lipolysis by inhibiting its HSF-1-dependent expression. The apparent antagonism of SIR-2.1 and HSF-1, distinct from their synergism at heat shock promoters suggests a context-specific regulation of HSF-1 by SIR-2.1. We demonstrate that the SIR-2.1 and protein kinase A pathways are both indispensable, and independently converge on ATGL-1 for lipolysis. HSF-1 activation by proteostasis disturbances inhibits starvation-induced lipid mobilization, whereas its age-related decline limits fat deposition through atgl-1. Our findings reveal a crosstalk between proteostasis and lipid/energy metabolism, which may modulate stress resilience and aging.

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Section: Discussionmentioning

confidence: 99%

An intestinal Sir2-HSF1-ATGL1 pathway regulates lipolysis inC. elegans

Somogyvári,

Khatatneh,

Hajdú

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Recent genetic studies have provided invaluable resources for understanding the molecular details of stress-induced transcriptional reprogramming and for discovering new therapeutics targeting the heat shock response. 1 , 40 , 41 However, the current data originate predominantly from cancer cell lines and tumor samples that are not adequate in portraying the importance of HSFs benign human tissues. To increase our understanding of the role of HSFs in human physiology and organismal homeostasis, we investigated the cell-type specific expression and localization patterns of HSFs in a comprehensive selection of human tissue samples with immunohistochemistry.…”

Section: Discussionmentioning

confidence: 99%