Open AccessPerinuclear mitochondrial clustering, increased ROS levels, and HIF1 are required for the activation of HSF1 by heat stress
Author(s) -
Saloni Agarwal,
Subramaniam Ganesh
Publication year - 2020
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.245589
Subject(s) - hsf1 , biology , heat shock factor , microbiology and biotechnology , mitochondrion , heat shock , transcription factor , heat shock protein , reactive oxygen species , hsp70 , biochemistry , gene
Heat shock response (HSR) is a conserved cellular defensive response against stresses such as temperature, oxidative stress, and heavy metals. A significant group of players in HSR is the set of molecular chaperones, known as heat shock proteins (HSPs) that assist in the refolding of unfolded proteins and prevent the accumulation of damaged proteins. HSP genes are activated by the HSF1 transcription factor−a master regulator of the HSR pathway. A variety of stressors activates HSF1, but the key molecular players and the process that directly contribute to the HSF1 activation remains unclear. In this study, we show that heat shock induces perinuclear clustering of mitochondria in mammalian cells, and this clustering is essential for the activation of HSR. We also show that this perinuclear clustering of mitochondria results in the increased levels of ROS in the nucleus, leading to the activation of hypoxia-inducible factor-1α (HIF-1α). Finally, we provide evidence to suggest that HIF-1α is one of the critical regulators of HSF1 and that HIF-1α is essential for the activation of HSR during a heat shock.