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

Autor: Akira Nakai, Mitsuaki Fujimoto, Mariko Okada, Pratibha Srivastava, Ryosuke Takii, Ai Kurashima, Arpit Katiyar, Ke Tan
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
heat shock protein
Mitochondrion
HSF1
General Biochemistry
Genetics and Molecular Biology
Mitochondrial Proteins
03 medical and health sciences
Mice
proteotoxic stress
0302 clinical medicine
Heat Shock Transcription Factors
Mitochondrial unfolded protein response
Heat shock protein
Animals
Humans
Phosphorylation
Promoter Regions
Genetic
lcsh:QH301-705.5
Research Articles
Membrane Potential
Mitochondrial
Chaperone Gene
proteostasis
biology
Chemistry
fungi
Fibroblasts
Recombinant Proteins
Cell biology
DNA-Binding Proteins
mitochondria
030104 developmental biology
Proteostasis
HEK293 Cells
lcsh:Biology (General)
030220 oncology & carcinogenesis
Chaperone (protein)
Gene Knockdown Techniques
biology.protein
Unfolded Protein Response
HSP60
RNA Interference
SSBP1
Research Article
HeLa Cells
Molecular Chaperones
Zdroj: FEBS Open Bio, Vol 10, Iss 6, Pp 1135-1148 (2020)
FEBS Open Bio
ISSN: 2211-5463
Popis: 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.
The mitochondrial unfolded protein response (UPRmt) 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 UPRmt.
Databáze: OpenAIRE
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