Oliver's mTOR Atlas Evidence Platform
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Transient APC/C inactivation by mTOR boosts glycolysis during cell cycle entry

Paul D, Bolhuis DL, Yan H, Das S, Xu X, Abbate CC, Jenkins LMM, Emanuele MJ, Andresson T, Huang J, Albeck JG, …, Cappell SD · 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

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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 type5 - Mechanistic / In Vitro
Model systemMammalian cells entering the cell cycle after mitogen stimulation
JournalNature
Year2025
Peer reviewedYes
Record last updated2026-10-01
SourceDOI 10.1038/s41586-025-09328-w · PMID 40739344 · Free full text (PMC12488482)

Where this study fits

How this study connects to the pathway map, open questions, people and other studies in the Atlas.

People in the Atlas

  • Debasish Paul first author · 1 study in the Atlas

    Postdoctoral fellow in Steven Cappell's lab at the National Cancer Institute who studies how ubiquitin ligases time the start of the cell cycle, and who found that mTOR briefly switches off the APC/C to give cells a burst of glycolysis as they start to divide

  • Steven D. Cappell last author · 1 study in the Atlas

    Studies how single cells commit to dividing; showed that mTOR briefly switches off the APC/C to give cells a pulse of glycolysis at cell cycle entry

  • John G. Albeck 2 studies in the Atlas

    Measures mTORC1, AMPK and other metabolic signals in single living cells, following how they change over minutes and hours

More: 10 other authors

No profile yet: Bolhuis DL, Yan H, Das S, Xu X, Abbate CC, Jenkins LMM, Emanuele MJ, Andresson T, Huang J, Brown NG

Related studies

More related studies

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Topics

mTORPFKFB3

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

InterventionMitogen stimulation; mTOR / phosphatase perturbation
TargetmTOR / APC/C-CDH1 / PFKFB3
ModelHuman & mouse cells
EffectmTOR transiently inactivates APC/C at cell cycle entry, producing a required pulse of glycolysis

Cite this paper

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Paul, D., Bolhuis, D. L., Yan, H., Das, S., Xu, X., Abbate, C. C., Jenkins, L. M. M., Emanuele, M. J., Andresson, T., Huang, J., Albeck, J. G., Brown, N. G., & Cappell, S. D. (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 Bolhuis, D. L. and Yan, H. and Das, S. and Xu, X. and Abbate, C. C. and Jenkins, L. M. M. and Emanuele, M. J. and Andresson, T. and Huang, J. and Albeck, J. G. and Brown, N. G. and Cappell, S. D.},
  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}
}
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