Transient APC/C inactivation by mTOR boosts glycolysis during cell cycle entry

Area of Science:

• Cell Biology
• Metabolism
• Biochemistry

Background:

• Cell cycle entry requires rapid ATP and biosynthesis, favoring glycolysis.
• The anaphase-promoting complex/cyclosome (APC/C) regulates cell division but paradoxically inhibits glycolysis.
• Coordinated regulation of cell cycle and metabolism is crucial for cell division.

Purpose of the Study:

• To investigate how mammalian cells coordinate cell cycle entry with metabolic demands.
• To elucidate the mechanism by which glycolysis is favored during cell cycle progression despite APC/C activity.

Main Methods:

• Investigated the role of APC/C^CDH1 activity in regulating glycolysis during cell cycle entry.
• Utilized mammalian cell models to study the effects of mitogen stimulation on APC/C and glycolytic enzyme levels.
• Examined the impact of mTOR-mediated CDH1 phosphorylation on APC/C function and PFKFB3 accumulation.

Main Results:

• Transient inactivation of APC/C during cell cycle entry allows a metabolic shift towards glycolysis.
• Mitogen stimulation triggers mTOR-mediated CDH1 phosphorylation, leading to partial APC/C inactivation.
• This inactivation stabilizes PFKFB3, a key glycolytic enzyme, enhancing glycolysis for biomass production.

Conclusions:

• Cells employ an incoherent feedforward loop involving transient APC/C inhibition to generate a glycolytic pulse for cell cycle entry.
• This mechanism ensures sufficient ATP and biosynthetic intermediates for rapid cell proliferation.
• The study reveals a novel coordination strategy between cell cycle progression and cellular metabolism.