Format

Send to

Choose Destination
Life Sci Alliance. 2020 Feb 6;3(3). pii: e201900576. doi: 10.26508/lsa.201900576. Print 2020 Mar.

ER-resident sensor PERK is essential for mitochondrial thermogenesis in brown adipose tissue.

Author information

1
Laboratory of Biochemistry and Molecular Biology, Department of Medical Sciences, University of Miyazaki, Miyazaki, Japan.
2
Laboratory of Bioanalytical Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
3
Division of Molecular Biology, Institute for Genome Research, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.
4
Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
5
Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
6
Genome Laboratory, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
7
Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
8
Department of Pathological Cell Biology, Medical Research Institute, TMDU, Tokyo, Japan.
9
Department of Clinical Proteomics, National Cancer Center Research Institute, Tokyo, Japan.
10
Division of Pediatrics, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
11
Laboratory of Biochemistry and Molecular Biology, Department of Medical Sciences, University of Miyazaki, Miyazaki, Japan nishitoh@med.miyazaki-u.ac.jp.

Abstract

Mitochondria play a central role in the function of brown adipocytes (BAs). Although mitochondrial biogenesis, which is indispensable for thermogenesis, is regulated by coordination between nuclear DNA transcription and mitochondrial DNA transcription, the molecular mechanisms of mitochondrial development during BA differentiation are largely unknown. Here, we show the importance of the ER-resident sensor PKR-like ER kinase (PERK) in the mitochondrial thermogenesis of brown adipose tissue. During BA differentiation, PERK is physiologically phosphorylated independently of the ER stress. This PERK phosphorylation induces transcriptional activation by GA-binding protein transcription factor α subunit (GABPα), which is required for mitochondrial inner membrane protein biogenesis, and this novel role of PERK is involved in maintaining the body temperatures of mice during cold exposure. Our findings demonstrate that mitochondrial development regulated by the PERK-GABPα axis is indispensable for thermogenesis in brown adipose tissue.

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center