PT  - JOURNAL ARTICLE
AU  - Kato, Hironori
AU  - Okabe, Kohki
AU  - Miyake, Masato
AU  - Hattori, Kazuki
AU  - Fukaya, Tomohiro
AU  - Tanimoto, Kousuke
AU  - Beini, Shi
AU  - Mizuguchi, Mariko
AU  - Torii, Satoru
AU  - Arakawa, Satoko
AU  - Ono, Masaya
AU  - Saito, Yusuke
AU  - Sugiyama, Takashi
AU  - Funatsu, Takashi
AU  - Sato, Katsuaki
AU  - Shimizu, Shigeomi
AU  - Oyadomari, Seiichi
AU  - Ichijo, Hidenori
AU  - Kadowaki, Hisae
AU  - Nishitoh, Hideki
TI  - ER-resident sensor PERK is essential for mitochondrial thermogenesis in brown adipose tissue
AID  - 10.26508/lsa.201900576
DP  - 2020 Mar 01
TA  - Life Science Alliance
PG  - e201900576
VI  - 3
IP  - 3
4099  - https://www.life-science-alliance.org/content/3/3/e201900576.short
4100  - https://www.life-science-alliance.org/content/3/3/e201900576.full
SO  - Life Sci. Alliance2020 Mar 01; 3
AB  - 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.