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Malonyl-CoA is a conserved endogenous ATP-competitive mTORC1 inhibitor

Nicastro R, Brohée L, Alba J, Nüchel J, Figlia G, Kipschull S, Gollwitzer P, Romero-Pozuelo J, Fernandes SA, Lamprakis A, Vanni S, Teleman AA · 2023 · Nature Cell Biology · Atlas ID NIC2023

What this study shows

Malonyl-CoA, an intermediate of fatty-acid biosynthesis, binds the mTOR catalytic pocket directly and acts as a conserved ATP-competitive inhibitor of mTORC1; when fatty acid synthase is downregulated, rising malonyl-CoA feeds back to dampen mTORC1 activity, linking lipogenic capacity to overall biosynthetic output.

Abstract

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Cell growth is regulated by the mammalian/mechanistic target of rapamycin complex 1 (mTORC1), which functions both as a nutrient sensor and a master controller of virtually all biosynthetic pathways. This ensures that cells are metabolically active only when conditions are optimal for growth. Notably, although mTORC1 is known to regulate fatty acid biosynthesis, how and whether the cellular lipid biosynthetic capacity signals back to fine-tune mTORC1 activity remains poorly understood.

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At a glance

Evidence type M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Yeast and mammalian cells) 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 systemYeast and mammalian cells
JournalNature Cell Biology
Year2023
Peer reviewedYes
Record last updated2026-09-23
SourceDOI 10.1038/s41556-023-01198-6 · PMID 37563253

In the Atlas

Related topics

Malonyl-CoA

Cite this paper

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Nicastro, R., Brohée, L., Alba, J., Nüchel, J., Figlia, G., Kipschull, S., Gollwitzer, P., Romero-Pozuelo, J., Fernandes, S. A., Lamprakis, A., Vanni, S., Teleman, A. A., De Virgilio, C., & Demetriades, C. (2023). Malonyl-CoA is a conserved endogenous ATP-competitive mTORC1 inhibitor. Nature Cell Biology. https://doi.org/10.1038/s41556-023-01198-6

@article{NIC2023,
  author       = {Nicastro, R. and Brohée, L. and Alba, J. and Nüchel, J. and Figlia, G. and Kipschull, S. and Gollwitzer, P. and Romero-Pozuelo, J. and Fernandes, S. A. and Lamprakis, A. and Vanni, S. and Teleman, A. A. and De Virgilio, C. and Demetriades, C.},
  title        = {{Malonyl-CoA is a conserved endogenous ATP-competitive mTORC1 inhibitor}},
  journal      = {Nature Cell Biology},
  year         = {2023},
  doi          = {10.1038/s41556-023-01198-6},
  note         = {PMID: 37563253},
}

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 NIC2023) [Data set]. https://mtor-atlas.org/study/NIC2023/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_NIC2023,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record NIC2023},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/NIC2023/},
  doi          = {10.5281/zenodo.22059963}
}