Oliver's mTOR Atlas Evidence Platform
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Pathway link CHOL-LYCHOS

Cholesterol LYCHOS (GPR155)

Cholesterol activates LYCHOS (GPR155).

Cholesterol itself sticks to the sensor. That is what tells the sensor there is plenty about: break the spot where it sticks and the growth signal no longer goes through, even though the sensor is still there. The reading is taken at the lysosome, where cholesterol arrives, not at the outside of the cell.

Cholesterol binds the amino-terminal permease-like region of LYCHOS, and that is the step the sensing depends on: mutating the binding site impairs mTORC1 activation while leaving the protein in place (SHI2022). Occupancy switches LYCHOS into the state that holds GATOR1, so the sterol is read where it accumulates, on the lysosome, rather than at the cell surface.

The conditions it holds under

Single-study edge in this corpus (SHI2022): human cell lines, photoaffinity and mutational biochemistry. The binding site was later resolved by cryo-EM outside this corpus (Bayly-Jones 2024, PMID 39358511; Zhao 2025, PMID 39824976; Li 2025, PMID 41058362). What is shown is that occupancy of the site is required for cholesterol-driven mTORC1 activation in cultured cells; no dose-response in tissue, no animal or human endpoint, and no measurement of how this route divides the signal with the SLC38A9-NPC1 complex (CAS2017).

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
emerging, few independent studies

Studies behind it

YearEvidenceStudy
2022 M Lysosomal GPCR-like protein LYCHOS signals cholesterol sufficiency to mTORC1SHI2022 Identifies LYCHOS (previously annotated GPR155) as a lysosomal cholesterol sensor for mTORC1. Cholesterol binds the amino-terminal permease-like region; mutating that site impairs mTORC1 activation. At high cholesterol LYCHOS binds GATOR1 through a conserved cytoplasm-facing loop, and by sequestering GATOR1 it promotes cholesterol- and Rag-dependent recruitment of mTORC1 to the lysosome. Boundary: human cell lines and biochemistry, not an organismal phenotype.

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.

“How settled” describes how far researchers in the field agree. It is not the same as the sign-off above, which only says whether a named curator has checked this page.

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