HSF1 is required for induction of mitochondrial chaperones during the mitochondrial unfolded protein response

Abstract

The mitochondrial unfolded protein response (UPRmt) is characterized by the transcriptional induction of mitochondrial chaperone and protease genes in response to impaired mitochondrial proteostasis and is regulated by ATF5 and CHOP in mammalian cells. However, the detailed mechanisms underlying the UPRmt are currently unclear. Here, we show that HSF1 is required for activation of mitochondrial chaperone genes, including HSP60, HSP10, and mtHSP70, in mouse embryonic fibroblasts during inhibition of matrix chaperone TRAP1, protease Lon, or electron transfer complex 1 activity. HSF1 bound constitutively to mitochondrial chaperone gene promoters, and we observed that its occupancy was remarkably enhanced at different levels during the UPRmt. Furthermore, HSF1 supported the maintenance of mitochondrial function under the same conditions. These results demonstrate that HSF1 is required for induction of mitochondrial chaperones during the UPRmt, and thus, it may be one of the guardians of mitochondrial function under conditions of impaired mitochondrial proteostasis.

Genome-Wide Role of HSF1 in Transcriptional Regulation of Desiccation Tolerance in the Anhydrobiotic Cell Line, Pv11

“…HSP genes in P. vanderplanki were predicted by the presence of HSP-related domains, including IPR013126, IPR031107, IPR008978, IPR001623, IPR002423, IPR003594, IPR001404, and blastp against Hspd1 (Hsp60), Hspe1 (Hsp10), and Hspa9 (mtHsp70) [ 59 ]. Additional filters for HSPs were based on molecular weight similarity to each group of HSPs, i.e., HSP10, HSP20, HSP40, HSP60, HSP70 and HSP90 ( Data S9 ).…”

The Mitochondrial Hsp90 TRAP1 and Alzheimer’s Disease

“…Hence, inhibition of TRAP1 causes an increase in calcium release, activating calcineurin and decreasing HSF1 migration. In turn, TRAP1-KO increases transcription of mitochondrial chaperone genes by HSF1, which suggests HSF1 to be a potential guardian of mitochondrial function upon impaired proteostasis (Katiyar et al, 2020).…”

Steering towards success in stormy times: FEBS Open Bio in 2021

“…Our median times to first and final decision have decreased in 2020 as compared to 2019 (as discussed further below), in line with our commitment to providing rapid and thorough peer review. Furthermore, downloads of our articles continue to rise dramatically: in addition to the articles mentioned above, other well‐downloaded articles this year include a report that the histone demethylase KDM3B protects against ferroptosis via SLC7A11 [13] and a study of the role of HSF1 in the mitochondrial unfolded protein response [14]. The authors are free to post the final version of record of their article in any repository they like, thereby helping to boost the visibility of articles published in FEBS Open Bio .…”