RT Journal Article SR Electronic T1 ER-resident sensor PERK is essential for mitochondrial thermogenesis in brown adipose tissue JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e201900576 DO 10.26508/lsa.201900576 VO 3 IS 3 A1 Kato, Hironori A1 Okabe, Kohki A1 Miyake, Masato A1 Hattori, Kazuki A1 Fukaya, Tomohiro A1 Tanimoto, Kousuke A1 Beini, Shi A1 Mizuguchi, Mariko A1 Torii, Satoru A1 Arakawa, Satoko A1 Ono, Masaya A1 Saito, Yusuke A1 Sugiyama, Takashi A1 Funatsu, Takashi A1 Sato, Katsuaki A1 Shimizu, Shigeomi A1 Oyadomari, Seiichi A1 Ichijo, Hidenori A1 Kadowaki, Hisae A1 Nishitoh, Hideki YR 2020 UL http://www.life-science-alliance.org/content/3/3/e201900576.abstract 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.