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

Paul D, Cappell SD et al. · 2025 · Nature · Atlas ID PAU2025

What this study shows

After mitogen stimulation, mTOR quickly phosphorylates the APC/C adaptor CDH1, partly releasing it and briefly inactivating APC/C; the glycolytic enzyme PFKFB3 accumulates and glycolysis rises, until a delayed phosphatase restores APC/C. This incoherent feed-forward loop produces a pulse of glycolysis that cell cycle entry requires.

Abstract

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Mammalian cells entering the cell cycle favour glycolysis to rapidly generate ATP and produce the biosynthetic intermediates that are required for rapid biomass accumulation. Simultaneously, the ubiquitin-ligase anaphase-promoting complex/cyclosome and its coactivator CDH1 (APC/C) remains active, allowing origin licensing and blocking premature DNA replication. Paradoxically, glycolysis is reduced by APC/C through the degradation of key glycolytic enzymes, raising the question of how cells coordinate these mutually exclusive events to ensure proper cell division.

Read the full abstract on PubMed →

At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Mammalian cells entering the cell cycle after mitogen stimulation) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Mammalian cells entering the cell cycle after mitogen stimulation
Journal	Nature
Year	2025
Peer reviewed	Yes
Record last updated	2026-09-23
Source	DOI 10.1038/s41586-025-09328-w · PMID 40739344 · Free full text (PMC12488482)

Extracted findings

Intervention	Mitogen stimulation; mTOR / phosphatase perturbation
Target	mTOR / APC/C-CDH1 / PFKFB3
Model	Human & mouse cells
Effect	mTOR transiently inactivates APC/C at cell cycle entry, producing a required pulse of glycolysis

Cite this paper

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Paul, D., et al. (2025). Transient APC/C inactivation by mTOR boosts glycolysis during cell cycle entry. Nature. https://doi.org/10.1038/s41586-025-09328-w

@article{PAU2025,
  author       = {Paul, D. and Cappell, S. D. and others},
  title        = {{Transient APC/C inactivation by mTOR boosts glycolysis during cell cycle entry}},
  journal      = {Nature},
  year         = {2025},
  doi          = {10.1038/s41586-025-09328-w},
  note         = {PMID: 40739344},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record PAU2025) [Data set]. https://mtor-atlas.org/study/PAU2025/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_PAU2025,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record PAU2025},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/PAU2025/},
  doi          = {10.5281/zenodo.22059963}
}