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.