TY - JOUR T1 - ER-resident sensor PERK is essential for mitochondrial thermogenesis in brown adipose tissue JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201900576 VL - 3 IS - 3 SP - e201900576 AU - Hironori Kato AU - Kohki Okabe AU - Masato Miyake AU - Kazuki Hattori AU - Tomohiro Fukaya AU - Kousuke Tanimoto AU - Shi Beini AU - Mariko Mizuguchi AU - Satoru Torii AU - Satoko Arakawa AU - Masaya Ono AU - Yusuke Saito AU - Takashi Sugiyama AU - Takashi Funatsu AU - Katsuaki Sato AU - Shigeomi Shimizu AU - Seiichi Oyadomari AU - Hidenori Ichijo AU - Hisae Kadowaki AU - Hideki Nishitoh Y1 - 2020/03/01 UR - https://www.life-science-alliance.org/content/3/3/e201900576.abstract N2 - 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. ER -