v-ATPase

Gene/Protein · 4 studies in the Atlas

Vacuolar H+-ATPase. Necessary for amino acids to activate mTORC1, and it makes extensive amino-acid-sensitive contacts with Ragulator, but it is not itself the sensor: the Atlas assigns that role to SLC38A9, Sestrin2 and SAMTOR for their respective inputs. ATP hydrolysis by the pump is required for amino acids to regulate the v-ATPase-Ragulator interaction, which is the evidence the signal begins inside the lysosomal lumen (Zoncu 2011, PMID 22053050).

The pump the sensing machinery is built on. A proton pump on the lysosome. Amino acids cannot switch mTORC1 on without it, and it touches the Ragulator machinery in a way that changes with amino-acid levels - but it is not the thing that reads the amino acids. Other proteins do the reading; this one has to be working for the message to get out.

Required for amino-acid signalling; inhibitor experiments cannot fully separate the signalling role from loss of lysosomal acidification.

TL;DR. v-ATPase appears in 4 curated studies in Oliver's mTOR Atlas: 4 at the molecular level (cells, biochemistry, structure). No study in people is recorded for it in the Atlas yet. It has 1 interaction in the curated pathway model.

In the pathway model

1 interaction in the curated mTOR pathway model. Each row is a claim with the evidence behind it; the evidence code is the kind of study, not its quality.

Interaction	Mechanism	Evidence	Studies
v-ATPase required-for Ragulator mechanism: binding · this link in full · on the map table	The lysosome's acid pump senses amino acids from the inside and passes that information out to Ragulator, which passes it on to the Rag proteins. The lysosome's proton pump talks to Ragulator from the inside out: amino acids inside the lysosome change v-ATPase, which changes Ragulator, which changes the Rags. The lysosome's proton pump talks to Ragulator from the inside out: amino acids inside the lysosome change v-ATPase, which changes Ragulator, which changes the Rags. Holds under: The 'inside-out' model requires amino acids to accumulate inside the lysosome first; how they get there for every amino acid is not fully mapped. plausible in people, not shown directly · emerging, few independent studies	M	ZON2011, BAR2012

Evidence at a glance

Evidence	What it means	Studies
M	Molecular — cells, biochemistry, structure	4

No direct human evidence in the Atlas for this entity yet — everything below rests on animal or molecular work.

Studies

Year	Evidence	Study
2026	M	A TBK1/ULK1 signalling axis couples lysosomal stress to TFEB activation. ESP2026 Identifies a nutrient-independent lysosomal pathway in which v-ATPase recruits TBK1/ULK1 to phosphorylate FNIP1, inhibiting the FLCN:FNIP complex and releasing TFEB for nuclear translocation; recurrent ATP6V1B2 mutations found in follicular lymphoma patients constitutively hyperactivate this axis, driving TFEB-dependent tumor proliferation.
2017	M	Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes ABU2017 Turns the lysosome from a place where mTORC1 is switched on into something mTORC1 also controls: inhibiting mTOR strongly reduces the efflux of most essential amino acids out of the lysosome, so the organelle becomes a store rather than a source. Measured directly by rapidly isolating lysosomes and profiling their contents, which is why the claim is about concentrations inside the organelle and not inferred from signalling readouts. Boundary: one human cell line, acute pharmacological inhibition.
2016	M	Dynamics of mTORC1 activation in response to amino acids MAN2016 Live imaging shows mTORC1 moves to lysosomes within 2 minutes of amino acid addition and peaks by 5 minutes, in step with leucine arriving in lysosomes; phosphorylation of classic mTORC1 targets lags behind, suggesting mTORC1 passes briefly through the lysosome before acting on substrates elsewhere.
2011	M	mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase ZON2011 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.

Related entities

Lysosome 4 mTORC1 2 Torin1 1 ULK1 1 TFEB 1 Raptor 1 mTOR 1 Leucine 1 Rag GTPases 1 Sestrin2 1 FLCN / FNIP1/2 1 Ragulator 1

Cite this page

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Barton, O. (2026). v-ATPase [Entity page]. In Oliver's mTOR Atlas [Data set]. https://mtor-atlas.org/gene/v-atpase/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_gene_v_atpase,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}: v-ATPase},
  howpublished = {Entity page in a data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/gene/v-atpase/},
  doi          = {10.5281/zenodo.22059963}
}

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