Pathway link LYSO-MTORC1
Lysosome mTORC1
Lysosome required-for mTORC1.
In the amino-acid route, mTORC1 has to travel to the lysosome before it can work, because its activator Rheb waits there. Getting it there and switching it on are two different steps: when researchers glued mTORC1 to the lysosome so it no longer had to be delivered, amino acids stopped making any difference, but the activator was still needed.
The conditions it holds under
Scoped to amino-acid-driven activation. Live BRET imaging in this corpus (BOU2020) resolves mTOR activity in the cytosol, at the lysosome, in the nucleus and near mitochondria, so mTOR signalling is measurably not one pool. This map draws the lysosomal route and keeps the other localisations declared as open rather than asserting there are none. FER2024 refines this further: lysosomal mTORC1 (fed by local lysosomal proteolysis) and cytoplasmic mTORC1 (fed by exogenous amino acids) phosphorylate distinct downstream substrates — the lysosome is required for one regulatory sub-pool of mTORC1, not for all of it.
- Time it takes
- minutes
- Step
- direct (one molecule acts on the other)
- Measured in
- human cells
- Where in the cell
- lysosome
- Reaches people?
- plausible in people, not shown directly
- How settled
- settled in the literature
Studies behind it
| Year | Evidence | Study |
|---|---|---|
| 2010 | M | Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acidsSAN2010 Established WHERE mTORC1 gets switched on: the lysosome surface. Identified Ragulator as the lysosomal dock that recruits the Rag GTPases and drags mTORC1 to the membrane where its activator Rheb lives. Amino acids work by controlling this translocation. |
| 2011 | M | mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPaseZON2011 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. |
| 2024 | M | Spatial and functional separation of mTORC1 signalling in response to different amino acid sourcesFER2024 mTORC1 regulation and downstream substrate phosphorylation are spatially separated: lysosomal mTORC1 (fed by local lysosomal proteolysis) and cytoplasmic mTORC1 (fed by exogenous amino acids) phosphorylate distinct substrates depending on amino acid source, challenging the single lysosomal-hub model. |
| 2011 | M | Lysosomal positioning coordinates cellular nutrient responsesKOR2011 Where the lysosome sits inside the cell helps decide whether mTORC1 is on. With nutrients available, lysosomes move to the cell periphery, physically close to the plasma-membrane signalling modules, and mTORC1 is active there; starvation changes intracellular pH and pulls lysosomes into a cluster around the nucleus, where mTORC1 output falls and autophagy is released. Lysosomal position also sets the rate of autophagosome-lysosome fusion, so one variable acts at both the initiation and the termination end of autophagic flux. This added a spatial axis to mTORC1 regulation that Rag/Ragulator recruitment alone does not account for. |
| 2025 | M | Structural basis for mTORC1 activation on the lysosomal membraneCUI2025 Resolves how mTORC1 flips from 'parked on the lysosome' to 'catalytically switched on'. Reconstituting the whole assembly on membranes from purified Rheb, Rag GTPases, Ragulator and mTORC1, cryo-EM shows the kinase reaches full activity only after two separate anchoring steps: Rag-Ragulator first pulls it to within about 100 angstroms of the membrane, then Rheb pulls it to within about 40 angstroms, and only when Raptor and mTOR itself also touch the membrane directly do the catalytic residues line up for full activity. Growth-factor input (via Rheb) and nutrient input (via the Rags) are shown converging on the same physical docking event rather than acting through separate switches. Boundary: reconstituted on synthetic membranes from purified components — a structural/biochemical model, not a measurement inside a living cell. |
Points the other way
No study in the Atlas contradicts this link. That means none in this curated set, not none in the literature.
Who has checked this
- Checked by
- No researcher outside the project has checked this link yet.
- Curator sign-off
- Not signed off yet. This link was drafted with AI help and has not been reviewed link by link; treat it as a proposal until it is.
- Curated by
- Oliver Barton, with AI help for drafting; see how links are checked.
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