Oliver's mTOR Atlas Evidence Platform
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mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase

Zoncu R, Bar-Peled L, Efeyan A, Wang S, Sancak Y, Sabatini DM · 2011 · Science · Atlas ID ZON2011

What this study shows

Showed amino acid sensing starts INSIDE the lysosome: amino acids accumulate in the lumen and the v-ATPase relays that signal outward ('inside-out') to Ragulator-Rag. A surprising twist on where the cell measures its nutrient status.

Abstract

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The mTOR complex 1 (mTORC1) protein kinase is a master growth regulator that is stimulated by amino acids. Amino acids activate the Rag guanosine triphosphatases (GTPases), which promote the translocation of mTORC1 to the lysosomal surface, the site of mTORC1 activation. We found that the vacuolar H(+)-adenosine triphosphatase ATPase (v-ATPase) is necessary for amino acids to activate mTORC1. The v-ATPase engages in extensive amino acid-sensitive interactions with the Ragulator, a scaffolding complex that anchors the Rag GTPases to the lysosome.

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 cells + cell-free reconstitution) 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 cells + cell-free reconstitution
JournalScience
Year2011
Peer reviewedYes
Record last updated2026-08-22
SourceDOI 10.1126/science.1207056 · PMID 22053050 · Free full text (PMC3211112)

Extracted findings

InterventionBiochemical/genetic (v-ATPase)
Targetv-ATPase / Rag-Ragulator / mTORC1
ModelHuman cells + cell-free reconstitution
EffectmTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase

In the Atlas

Related topics

Lysosomev-ATPaseRag GTPasesmTORC1Ragulator

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Learn the biology

Want to understand the biology behind this study? → The Lysosome as a Signalling Platform

Cite this paper

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Zoncu, R., Bar-Peled, L., Efeyan, A., Wang, S., Sancak, Y., & Sabatini, D. M. (2011). mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase. Science. https://doi.org/10.1126/science.1207056

@article{ZON2011,
  author       = {Zoncu, R. and Bar-Peled, L. and Efeyan, A. and Wang, S. and Sancak, Y. and Sabatini, D. M.},
  title        = {{mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase}},
  journal      = {Science},
  year         = {2011},
  doi          = {10.1126/science.1207056},
  note         = {PMID: 22053050},
}

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 ZON2011) [Data set]. https://mtor-atlas.org/study/ZON2011/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_ZON2011,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record ZON2011},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/ZON2011/},
  doi          = {10.5281/zenodo.22059963}
}