Heat shock factor-1 alleviates ER-stress in Caenorhabditis elegans

TL;DR

Heat shock factor-1 helps cells manage endoplasmic reticulum stress in worms and human cells.

Contribution

HSF-1 is shown to regulate the UPRER, linking heat shock and ER stress responses.

Findings

HSF-1 is required for UPRER activation in C. elegans.

HSF-1 is needed for tolerance to ER stress induced by tunicamycin.

HSF-1 regulates UPRER-related genes in human cells.

Abstract

Cells can be exposed to many different stimuli that induce a variety of stresses, such as oxidative stress and proteotoxic stress of the cytoplasm, endoplasmic reticulum or mitochondria. These types of stresses trigger conserved molecular pathways (e.g., heat shock response, unfolded protein response, and autophagy) that can restore cellular homeostasis. Dysfunction (deficiency or hyperactivity) of these pathways is associated with aging and pathologies such as neurodegenerative diseases, diabetes and cancer. The basic molecular machinery of these stress response pathways has been elucidated, but how these pathways interact remains a vibrant area of research. Here, we show that the heat shock transcription factor-1 (HSF-1), the master regulator of the heat shock response, is required for efficient activation of the endoplasmic reticulum unfolded protein response (UPRER) in the nematode Caenorhabditis elegans. Tolerance against tunicamycin-induced ER stress also requires HSF-1 activity. We found that mRNA levels of several genes involved in the UPRER are regulated by HSF1 in human cell lines. These results suggest that HSF-1 plays a critical role in the cellular response to ER stress.

The online version contains supplementary material available at 10.1038/s41598-026-43060-3.

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