Oliver's mTOR Atlas Evidence Platform
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AMPK phosphorylation of raptor mediates a metabolic checkpoint

Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, Turk BE, Shaw RJ · 2008 · Molecular Cell · Atlas ID GWI2008

What this study shows

Found a SECOND way the energy sensor AMPK shuts mTORC1 down. Besides acting through TSC2, AMPK directly phosphorylates Raptor - the core mTORC1 subunit - to halt growth when energy runs low. This 'metabolic checkpoint' is exactly the switch that drugs like metformin and exercise tap into.

Abstract

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AMPK is a highly conserved sensor of cellular energy status that is activated under conditions of low intracellular ATP. AMPK responds to energy stress by suppressing cell growth and biosynthetic processes, in part through its inhibition of the rapamycin-sensitive mTOR (mTORC1) pathway. AMPK phosphorylation of the TSC2 tumor suppressor contributes to suppression of mTORC1; however, TSC2-deficient cells remain responsive to energy stress. Using a proteomic and bioinformatics approach, we sought to identify additional substrates of AMPK that mediate its effects on growth control.

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: Human/mouse 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 type5 - Mechanistic / In Vitro
Model systemHuman/mouse cells (biochemistry)
JournalMolecular Cell
Year2008
Peer reviewedYes
Record last updated2026-08-22
SourceDOI 10.1016/j.molcel.2008.03.003 · PMID 18439900 · Free full text (PMC2674027)

Extracted findings

InterventionBiochemical/genetic (AMPK phosphorylation of raptor)
Targetraptor / mTORC1 / AMPK
ModelHuman/mouse cells (biochemistry)
EffectUnder energy stress AMPK phosphorylates raptor → a metabolic checkpoint that suppresses mTORC1

In the Atlas

Related topics

TSC1/TSC2RaptormTORC1Energy & cellular stressAMPK

Open questions that cite this study

More studies on this topic

Cite this paper

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Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008). AMPK phosphorylation of raptor mediates a metabolic checkpoint. Molecular Cell. https://doi.org/10.1016/j.molcel.2008.03.003

@article{GWI2008,
  author       = {Gwinn, D. M. and Shackelford, D. B. and Egan, D. F. and Mihaylova, M. M. and Mery, A. and Vasquez, D. S. and Turk, B. E. and Shaw, R. J.},
  title        = {{AMPK phosphorylation of raptor mediates a metabolic checkpoint}},
  journal      = {Molecular Cell},
  year         = {2008},
  doi          = {10.1016/j.molcel.2008.03.003},
  note         = {PMID: 18439900},
}

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 GWI2008) [Data set]. https://mtor-atlas.org/study/GWI2008/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_GWI2008,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record GWI2008},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/GWI2008/},
  doi          = {10.5281/zenodo.22059963}
}