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A systems study reveals concurrent activation of AMPK and mTOR by amino acids

Dalle Pezze P, Ruf S, Sonntag AG, Langelaar-Makkinje M, Hall P, Heberle AM, Razquin Navas P, van Eunen K, Tölle RC, Schwarz JJ, Wiese H, …, Thedieck K · 2016 · Nature Communications · Atlas ID DAL2016

What this study shows

Adding amino acids back to starved cells switched on AMPK, PI3K and mTORC2 acutely and independently of mTORC1, at the same time as mTOR. AMPK activation ran through CaMKK-beta and, under amino acid sufficiency, AMPK kept autophagy going via ULK1. So the textbook picture of AMPK and mTORC1 as simple opposites does not hold in the first minutes after feeding - which matters for how the AMPK-ULK1 feedback arm behaves over time.

Abstract

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Amino acids (aa) are not only building blocks for proteins, but also signalling molecules, with the mammalian target of rapamycin complex 1 (mTORC1) acting as a key mediator. However, little is known about whether aa, independently of mTORC1, activate other kinases of the mTOR signalling network. To delineate aa-stimulated mTOR network dynamics, we here combine a computational-experimental approach with text mining-enhanced quantitative proteomics.

Read the full abstract on PubMed →

At a glance

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Evidence type M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human cell lines; amino acid re-addition time courses, quantitative proteomics and dynamic modelling) 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 cell lines; amino acid re-addition time courses, quantitative proteomics and dynamic modelling
JournalNature Communications
Year2016
Peer reviewedYes
Record last updated2026-10-01
SourceDOI 10.1038/ncomms13254 · PMID 27869123 · Free full text (PMC5121333)

Where this study fits

How this study connects to the pathway map, open questions, people and other studies in the Atlas.

Pathway relations

Supports

AMPK activates ULK1

Strongest evidence: M (Molecular — cells, biochemistry, structure) · disputed: at least one study points the other way · Status: Contested

plausible in people, not shown directly

Contested direction. EGA2010 and KIM2011 report activating phosphorylation. PAR2023 (Park, Lee and Kim, Nat Commun 2023, PMID 37225695) reports that under glucose starvation and mitochondrial energy stress AMPK inhibits ULK1 activation and…

People in the Atlas

  • Piero Dalle Pezze first author · 2 studies in the Atlas

    First author of two Atlas modelling studies: the dynamic insulin–mTOR network model (TSC-independent mTORC2) and the systems study of concurrent AMPK and mTOR activation by amino acids.

  • Kathrin Thedieck last author · 3 studies in the Atlas

    Senior author of three Atlas studies that treat mTOR signalling as a dynamic network: TSC-independent mTORC2 activation, concurrent AMPK and mTOR activation by amino acids, and G3BP tethering of TSC to lysosomes.

  • Annika G. Sonntag 2 studies in the Atlas

    Experimental researcher in the Thedieck group who contributed cell data to the dynamic mTOR network model and the AMPK–mTOR amino acid study.

  • Alexander M Heberle 2 studies in the Atlas

    Cell biologist and Junior Group Leader at the University of Innsbruck who studies how mTOR balances growth signalling and metabolism when cells are under stress, trained in Kathrin Thedieck's systems-biology group

  • Björn Stork 1 study in the Atlas

    Heisenberg Professor for the molecular biology of cellular stress responses at Heinrich Heine University Düsseldorf, who studies the ULK1 complex, the switch that starts autophagy, and how it is wired to the energy sensor AMPK and to mTOR

More: 15 other authors
  • Daryl P. Shanley 2 studies in the Atlas

    Systems biologist of ageing whose Newcastle modelling group built, with the Thedieck lab, the dynamic models of mTOR signalling in the Atlas.

No profile yet: Ruf S, Langelaar-Makkinje M, Hall P, Razquin Navas P, van Eunen K, Tölle RC, Schwarz JJ, Wiese H, Warscheid B, Deitersen J, Fäßler E, Schäuble S, Hahn U, Horvatovich P

Related studies

More related studies

All 212 studies on mTORC1

Topics

ULK1LeucinePI3KmTORC1AutophagyAMPKmTORC2

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.

InterventionAmino acid withdrawal and re-addition
TargetAMPK; PI3K; mTORC2; mTORC1; ULK1
ModelHuman cell lines
EffectAmino acids acutely co-activate AMPK and mTOR; AMPK sustains autophagy under amino acid sufficiency

Cite this paper

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Dalle Pezze, P., Ruf, S., Sonntag, A. G., Langelaar-Makkinje, M., Hall, P., Heberle, A. M., Razquin Navas, P., van Eunen, K., Tölle, R. C., Schwarz, J. J., Wiese, H., Warscheid, B., Deitersen, J., Stork, B., Fäßler, E., Schäuble, S., Hahn, U., Horvatovich, P., Shanley, D. P., & Thedieck, K. (2016). A systems study reveals concurrent activation of AMPK and mTOR by amino acids. Nature Communications. https://doi.org/10.1038/ncomms13254

@article{DAL2016,
  author       = {Dalle Pezze, P. and Ruf, S. and Sonntag, A. G. and Langelaar-Makkinje, M. and Hall, P. and Heberle, A. M. and Razquin Navas, P. and van Eunen, K. and Tölle, R. C. and Schwarz, J. J. and Wiese, H. and Warscheid, B. and Deitersen, J. and Stork, B. and Fäßler, E. and Schäuble, S. and Hahn, U. and Horvatovich, P. and Shanley, D. P. and Thedieck, K.},
  title        = {{A systems study reveals concurrent activation of AMPK and mTOR by amino acids}},
  journal      = {Nature Communications},
  year         = {2016},
  doi          = {10.1038/ncomms13254},
  note         = {PMID: 27869123},
}

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 DAL2016) [Data set]. https://mtor-atlas.org/study/DAL2016/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_DAL2016,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record DAL2016},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/DAL2016/},
  doi          = {10.5281/zenodo.22059963}
}
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