Open AccessHSF1 is required for induction of mitochondrial chaperones during the mitochondrial unfolded protein response
Author(s) -
Katiyar Arpit,
Fujimoto Mitsuaki,
Tan Ke,
Kurashima Ai,
Srivastava Pratibha,
Okada Mariko,
Takii Ryosuke,
Nakai Akira
Publication year - 2020
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12863
Subject(s) - proteostasis , hsf1 , chaperone (clinical) , dnaja3 , unfolded protein response , biology , microbiology and biotechnology , mitochondrial matrix , mitochondrion , hspa9 , xbp1 , hsp60 , heat shock protein , mitochondrial dna , gene , endoplasmic reticulum , mitochondrial fusion , hsp70 , genetics , biochemistry , rna , cytosol , enzyme , peptide sequence , medicine , pathology , rna splicing
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.