Circadian Rheb oscillation alters the dynamics of hepatic mTORC1 activity and mitochondrial morphology

FEBS Letters

article

Qiuyun Yuan¹  Mina Chen¹  Wanchun Yang¹  Bo Xiao³ 

[1] Neuroscience & Metabolism Research, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University;Department of Neurosurgery, West China Hospital, Sichuan University;Department of Biology, Southern University of Science and Technology

关键词: circadian clock;    DRP1;    mitochondrial dynamics;    Rheb/mTORC1;   

DOI  :  10.1002/1873-3468.14009

来源: John Wiley & Sons Ltd.

【 摘 要 】

The morphological structure and metabolic activity of mitochondria are coordinately regulated by circadian mechanisms. However, the mechanistic interplay between circadian mechanisms and mitochondrial architecture remains poorly understood. Here, we demonstrate circadian rhythmicity of Rheb protein in liver, in line with that of Per2. Using genetic mouse models, we show that Rheb, a small GTPase that binds mTOR, is critical for circadian oscillation of mTORC1 activity in liver. Disruption of Rheb oscillation in hepatocytes by persistent expression of Rheb transgene interrupted mTORC1 oscillation. We further show that Rheb-regulated mTORC1 altered mitochondrial fission factor DRP1 in liver, leading to altered mitochondrial dynamics. Our results suggest that Rheb/mTORC1 regulated DRP1 oscillation involves ubiquitin-mediated proteolysis. This study identifies Rheb as a nodal point that couples circadian clock and mitochondrial architecture for optimal mitochondrial metabolism.

【 授权许可】

Unknown