HSF1 is required for induction of mitochondrial chaperones during the mitochondrial unfolded protein response. Issue 6 (15th May 2020)

• Record Type: Journal Article
• Authors: Katiyar, Arpit; Fujimoto, Mitsuaki; Tan, Ke; Kurashima, Ai; Srivastava, Pratibha; Okada, Mariko; Takii, Ryosuke; Nakai, Akira
• Is Part Of: FEBS open bio. Volume 10:Issue 6(2020)
• Page Start: 1135
• Page End: 1148
• Publication Date: 2020-05-15
• Subjects: heat shock protein -- HSF1 -- mitochondria -- proteostasis -- proteotoxic stress -- SSBP1; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1002/2211-5463.12863
• Languages: English
• ISSNs: 2211-5463

Abstract

Abstract : The mitochondrial unfolded protein response (UPR mt ) 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 UPR mt 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 UPR mt . 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 UPR mt, and thus, it may be one of the guardians of mitochondrial function under conditions of impaired mitochondrial proteostasis. Abstract : The mitochondrial unfolded protein response (UPR mt ) is characterized by the transcriptional induction of mitochondrial chaperone and protease genes in response to impaired mitochondrial proteostasis. Here, we show that heat shock transcription factor (HSF1) is required for activation of mitochondrial chaperone genes and supports the maintenance of mitochondrial function in mouse cells during the UPR mt .