Mammalian TOR: a homeostatic ATP sensor

Dennis PB, Jaeschke A, Saitoh M, Fowler B, Kozma SC, Thomas G · 2001 · Science · Atlas ID DEN2001

What this study shows

The authors tested whether mTOR signalling responds to the cell's energy level, not only to amino acids. They reported that lowering intracellular ATP reduced signalling through the mTOR pathway, and that this happened independently of amino acid levels. Based on the kinase properties of mTOR, they proposed that mTOR itself senses ATP. Later work showed that much of the energy signal reaches mTORC1 through AMPK and TSC2, so the direct ATP-sensor model is one part of a larger picture. Boundary: cultured cells and in vitro kinase measurements; the ATP-sensor interpretation is the authors' model and has been revised by later AMPK work.

Abstract

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The bacterial macrolide rapamycin is an efficacious anticancer agent against solid tumors. In a hypoxic environment, the increase in mass of solid tumors is dependent on the recruitment of mitogens and nutrients. When nutrient concentrations change, particularly those of essential amino acids, the mammalian Target of Rapamycin (mTOR) functions in regulatory pathways that control ribosome biogenesis and cell growth. In bacteria, ribosome biogenesis is independently regulated by amino acids and adenosine triphosphate (ATP).

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: Cultured human cells (HEK293-type per MeSH 'Cell Line'); ATP lowering with 2-deoxyglucose and rotenone (per MeSH); in vitro mTOR kinase assays) 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	Cultured human cells (HEK293-type per MeSH 'Cell Line'); ATP lowering with 2-deoxyglucose and rotenone (per MeSH); in vitro mTOR kinase assays
Journal	Science
Year	2001
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1126/science.1063518 · PMID 11691993

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.

Intervention	Lowering intracellular ATP
Target	mTOR signalling (S6K1 readout per MeSH); mTOR kinase
Model	Human cell lines; in vitro
Effect	Lower ATP -> reduced mTOR pathway signalling

In the Atlas

Cite this paper

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Dennis, P. B., Jaeschke, A., Saitoh, M., Fowler, B., Kozma, S. C., & Thomas, G. (2001). Mammalian TOR: a homeostatic ATP sensor. Science. https://doi.org/10.1126/science.1063518

@article{DEN2001,
  author       = {Dennis, P. B. and Jaeschke, A. and Saitoh, M. and Fowler, B. and Kozma, S. C. and Thomas, G.},
  title        = {{Mammalian TOR: a homeostatic ATP sensor}},
  journal      = {Science},
  year         = {2001},
  doi          = {10.1126/science.1063518},
  note         = {PMID: 11691993},
}

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 DEN2001) [Data set]. https://mtor-atlas.org/study/DEN2001/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_DEN2001,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record DEN2001},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/DEN2001/},
  doi          = {10.5281/zenodo.22059963}
}

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