Lysosomal GPCR-like protein LYCHOS signals cholesterol sufficiency to mTORC1

Shin HR, Citron YR, Wang L, Tribouillard L, Goul CS, Stipp R, Sugasawa Y, Jain A, Samson N, Lim CY, Davis OB, …, Zoncu R · 2022 · Science · Atlas ID SHI2022

What this study shows

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.

Abstract

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Lysosomes coordinate cellular metabolism and growth upon sensing of essential nutrients, including cholesterol. Through bioinformatic analysis of lysosomal proteomes, we identified lysosomal cholesterol signaling (LYCHOS, previously annotated as G protein-coupled receptor 155), a multidomain transmembrane protein that enables cholesterol-dependent activation of the master growth regulator, the protein kinase mechanistic target of rapamycin complex 1 (mTORC1). Cholesterol bound to the amino-terminal permease-like region of LYCHOS, and mutating this site impaired mTORC1 activation.

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At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human cell lines (HEK293T, lysosomal proteomics); cholesterol-binding and GATOR1-binding assays) 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 type	5 - Mechanistic / In Vitro
Model system	Human cell lines (HEK293T, lysosomal proteomics); cholesterol-binding and GATOR1-binding assays
Journal	Science
Year	2022
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1126/science.abg6621 · PMID 36007018 · Free full text (PMC10023259)

In the Atlas

Links in the pathway map

Supports Cholesterol activates LYCHOS (GPR155)
Supports LYCHOS (GPR155) inhibits GATOR1

Cite this paper

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Shin, H. R., Citron, Y. R., Wang, L., Tribouillard, L., Goul, C. S., Stipp, R., Sugasawa, Y., Jain, A., Samson, N., Lim, C. Y., Davis, O. B., Castaneda-Carpio, D., Qian, M., Nomura, D. K., Perera, R. M., Park, E., Covey, D. F., Laplante, M., Evers, A. S., & Zoncu, R. (2022). Lysosomal GPCR-like protein LYCHOS signals cholesterol sufficiency to mTORC1. Science. https://doi.org/10.1126/science.abg6621

@article{SHI2022,
  author       = {Shin, H. R. and Citron, Y. R. and Wang, L. and Tribouillard, L. and Goul, C. S. and Stipp, R. and Sugasawa, Y. and Jain, A. and Samson, N. and Lim, C. Y. and Davis, O. B. and Castaneda-Carpio, D. and Qian, M. and Nomura, D. K. and Perera, R. M. and Park, E. and Covey, D. F. and Laplante, M. and Evers, A. S. and Zoncu, R.},
  title        = {{Lysosomal GPCR-like protein LYCHOS signals cholesterol sufficiency to mTORC1}},
  journal      = {Science},
  year         = {2022},
  doi          = {10.1126/science.abg6621},
  note         = {PMID: 36007018},
}

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 SHI2022) [Data set]. https://mtor-atlas.org/study/SHI2022/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_SHI2022,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record SHI2022},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/SHI2022/},
  doi          = {10.5281/zenodo.22059963}
}

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