ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS

Alexander A, Cai SL, Kim J, Nanez A, Sahin M, MacLean KH, Inoki K, Guan KL, Shen J, Person MD, Kusewitt D, …, Walker CL · 2010 · PNAS · Atlas ID ALE2010

What this study shows

Described a cytoplasmic job for the DNA-damage kinase ATM. In response to raised ROS, ATM activated TSC2 through LKB1 and AMPK, which repressed mTORC1 and induced autophagy. ATM-deficient cells had high ROS and poorly controlled mTORC1, and rapamycin lowered both and delayed lymphoma formation in Atm-deficient mice. Boundary: worked from the abstract only (PMC record without retrievable text); cell lines and mice. Note that the Atlas edge ROS-MTORC1 describes the opposite sign in another context, so the effect of ROS on mTORC1 depends on source and setting.

Abstract

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Ataxia-telangiectasia mutated (ATM) is a cellular damage sensor that coordinates the cell cycle with damage-response checkpoints and DNA repair to preserve genomic integrity. However, ATM also has been implicated in metabolic regulation, and ATM deficiency is associated with elevated reactive oxygen species (ROS). ROS has a central role in many physiological and pathophysiological processes including inflammation and chronic diseases such as atherosclerosis and cancer, underscoring the importance of cellular pathways involved in redox homeostasis.

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: Cell lines with ATM loss or ROS exposure; Atm-deficient mice treated with rapamycin) 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	Cell lines with ATM loss or ROS exposure; Atm-deficient mice treated with rapamycin
Journal	PNAS
Year	2010
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1073/pnas.0913860107 · PMID 20160076 · Free full text (PMC2840158)

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	ROS exposure; ATM deficiency; rapamycin
Target	ATM -> LKB1/AMPK -> TSC2 -> mTORC1
Model	Cell lines; Atm-deficient mice
Effect	ROS-activated ATM represses mTORC1 and induces autophagy; rapamycin rescues lymphomagenesis in Atm-null mice

In the Atlas

Cite this paper

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Alexander, A., Cai, S. L., Kim, J., Nanez, A., Sahin, M., MacLean, K. H., Inoki, K., Guan, K. L., Shen, J., Person, M. D., Kusewitt, D., Mills, G. B., Kastan, M. B., & Walker, C. L. (2010). ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. PNAS. https://doi.org/10.1073/pnas.0913860107

@article{ALE2010,
  author       = {Alexander, A. and Cai, S. L. and Kim, J. and Nanez, A. and Sahin, M. and MacLean, K. H. and Inoki, K. and Guan, K. L. and Shen, J. and Person, M. D. and Kusewitt, D. and Mills, G. B. and Kastan, M. B. and Walker, C. L.},
  title        = {{ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS}},
  journal      = {PNAS},
  year         = {2010},
  doi          = {10.1073/pnas.0913860107},
  note         = {PMID: 20160076},
}

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 ALE2010) [Data set]. https://mtor-atlas.org/study/ALE2010/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_ALE2010,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record ALE2010},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/ALE2010/},
  doi          = {10.5281/zenodo.22059963}
}

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