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Kickstart the cell cycle with a sugar boost: mTOR brake on APC/C-CDH1 triggers a glycolytic pulse

Fangxia Wang1, Yuu Kimata1

  • 1School of Life Science and Technology, ShanghaiTech University, Shanghai, China.

Developmental Cell
|October 7, 2025
PubMed

Insights

Cells exiting quiescence need to replicate DNA and boost metabolism. Mitogen-activated mTOR temporarily inhibits APC/C-CDH1, activating PFKFB3 for an energy surge that initiates cell proliferation.

Area of Science:

  • Cell biology
  • Molecular biology
  • Metabolism

Background:

  • Cellular quiescence is a state of reversible cell cycle arrest.
  • Exiting quiescence requires coordinated metabolic and DNA replication preparation.
  • The Anaphase-Promoting Complex/Cyclosome (APC/C) with Cdh1 (APC/C-CDH1) is a key regulator of cell cycle progression.

Purpose of the Study:

  • To investigate the molecular mechanisms linking cell cycle exit from quiescence to metabolic activation.
  • To elucidate the role of mTOR signaling in regulating metabolic enzymes during cell cycle re-entry.
  • To understand how APC/C-CDH1 activity is modulated during the transition from quiescence to proliferation.

Main Methods:

  • Cell culture models of quiescence and proliferation.
  • Western blotting to assess protein levels and phosphorylation.
  • Quantitative real-time PCR for gene expression analysis.
  • Metabolic assays to measure glycolysis rates.

Main Results:

  • Mitogen stimulation activates mTOR signaling.
  • Activated mTOR transiently suppresses the activity of APC/C-CDH1.
  • This suppression leads to the upregulation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a key glycolytic enzyme.
  • Increased PFKFB3 activity boosts glycolysis, providing ATP for proliferation.
  • APC/C-CDH1 activity is restored later, promoting cell cycle progression.

Conclusions:

  • Transient suppression of APC/C-CDH1 by mTOR is crucial for metabolic reprogramming during quiescence exit.
  • PFKFB3 acts as a critical mediator, linking cell cycle control to metabolic support for proliferation.
  • This regulatory axis ensures cells have sufficient energy before committing to DNA replication.

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