TSC2 mediates cellular energy response to control cell growth and survival

Inoki K, Zhu T, Guan KL · 2003 · Cell · Atlas ID INO2003

What this study shows

Established the energy-sensing arm of the pathway. When energy runs low, AMPK phosphorylates TSC2, boosting its ability to shut mTOR down - protecting the cell from burning through resources and from starvation-induced death. One of the founding papers for how mTOR reads the cell's fuel gauge (complements the Akt-TSC2 growth-factor arm).

Abstract

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Mutations in either the TSC1 or TSC2 tumor suppressor gene are responsible for Tuberous Sclerosis Complex. The gene products of TSC1 and TSC2 form a functional complex and inhibit the phosphorylation of S6K and 4EBP1, two key regulators of translation. Here, we describe that TSC2 is regulated by cellular energy levels and plays an essential role in the cellular energy response pathway. Under energy starvation conditions, the AMP-activated protein kinase (AMPK) phosphorylates TSC2 and enhances its activity.

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 (biochemistry)) 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 (biochemistry)
Journal	Cell
Year	2003
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1016/s0092-8674(03)00929-2 · PMID 14651849

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	Biochemical/genetic (AMPK/TSC2)
Target	TSC2 / AMPK / mTOR
Model	Mammalian cells (biochemistry)
Effect	TSC2 mediates the cellular energy response (via AMPK) to control cell growth and survival

In the Atlas

Links in the pathway map

Supports AMPK activates TSC1/TSC2

Learn the biology

Want to understand the biology behind this study? → The TSC Complex — Where the Inputs Meet

Cite this paper

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Inoki, K., Zhu, T., & Guan, K. L. (2003). TSC2 mediates cellular energy response to control cell growth and survival. Cell. https://doi.org/10.1016/s0092-8674(03)00929-2

@article{INO2003,
  author       = {Inoki, K. and Zhu, T. and Guan, K. L.},
  title        = {{TSC2 mediates cellular energy response to control cell growth and survival}},
  journal      = {Cell},
  year         = {2003},
  doi          = {10.1016/s0092-8674(03)00929-2},
  note         = {PMID: 14651849},
}

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 INO2003) [Data set]. https://mtor-atlas.org/study/INO2003/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_INO2003,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record INO2003},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/INO2003/},
  doi          = {10.5281/zenodo.22059963}
}

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