Crosstalk signaling between mitochondria and endoplasmic reticulum is essential for brown adipocyte function
Hironori Kato1, Hideki Nishitoh1*
1Laboratory of Biochemistry and Molecular Biology, Dept. of Medical Science, University of Miyazaki, Japan
Thermogenic function of brown adipose tissue is essential for survival of homeotherm. Energy consumption via thermogenesis from brown and beige adipocytes prevents metabolic disturbances in human. Although mitochondria play a central role in ATP production and thermogenesis in brown adipocytes, the molecular mechanism of mitochondrial quality control system remains unknown. Here we present the importance of mitochondria-endoplasmic reticulum (ER) crosstalk signaling in brown adipocyte function. The size of mitochondria is increased and that of ER is oppositely decreased during differentiation. Interestingly, the electron microscopic analysis revealed that the reduced ER was surrounded by expanded mitochondria and the area of ER-mitochondria contact site was increased in the differentiated brown adipocyte. During differentiation, the ER-resident sensor, PERK, was phosphorylated independently of ER stress-induced activation mechanism. The kinase activity of PERK was required for the maintenance of mitochondrial cristae structure and the expression of inner membrane proteins. Moreover, deletion of PERK impaired ATP generation through oxidative phosphorylation and β3 adrenergic receptor-mediated thermogenesis. Our findings suggest that PERK activation, which is mediated by mitochondria-ER crosstalk signaling, is essential for the mitochondrial quality control and function in brown adipocyte.
1. Kato H, Nishitoh H: Front. Oncol. 5:93 eCollection (2015)
2. Kadowaki H, Nagai A, Maruyama T, Takami Y, Satrimafitrah P, Kato H, Honda A, Hatta T, Natsume T, Sato T, Kai H, Ichijo H, Nishitoh H: Cell Rep. 13:944-956 (2015)
This study was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science