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

Qiuyun Yuan1, Mina Chen1, Wanchun Yang1,2

  • 1Neuroscience & Metabolism Research, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

FEBS Letters
|November 28, 2020
PubMed

Insights

This study reveals Rheb protein links the circadian clock to mitochondrial structure and function. Rheb regulates mTORC1 activity, impacting mitochondrial dynamics for optimal metabolism.

Area of Science:

  • Cell Biology
  • Chronobiology
  • Metabolism

Background:

  • Mitochondrial structure and metabolism are regulated by circadian rhythms.
  • The precise mechanisms linking circadian clocks to mitochondrial architecture are not fully understood.

Purpose of the Study:

  • To investigate the role of Rheb protein in the circadian regulation of mitochondrial dynamics.
  • To elucidate the interplay between circadian rhythms, Rheb, mTORC1, and mitochondrial fission.

Main Methods:

  • Utilized genetic mouse models to study Rheb oscillation and its effects.
  • Analyzed mTORC1 activity, DRP1 levels, and mitochondrial dynamics in liver tissue.
  • Investigated the role of ubiquitin-mediated proteolysis in Rheb/mTORC1 regulation of DRP1.

Main Results:

  • Demonstrated circadian rhythmicity of Rheb protein in the liver, correlating with Per2.
  • Showed Rheb is essential for circadian oscillation of mTORC1 activity in liver.
  • Found that Rheb-regulated mTORC1 impacts mitochondrial fission factor DRP1, altering mitochondrial dynamics.
  • Identified ubiquitin-mediated proteolysis as a key mechanism in Rheb/mTORC1-regulated DRP1 oscillation.

Conclusions:

  • Rheb acts as a crucial link between the circadian clock and mitochondrial architecture.
  • The Rheb/mTORC1 pathway regulates DRP1 oscillation, influencing mitochondrial dynamics.
  • This crosstalk is vital for maintaining optimal mitochondrial metabolism under circadian control.
Keywords:
DRP1Rheb/mTORC1circadian clockmitochondrial dynamics

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