mTORC1 is a master regulator of cell growth, which responds to nutrient availability — in particular, amino acids. Castellano et al. now show that mTORC1 is also regulated by cholesterol, suggesting a strong link between sterol metabolism and cell growth control. Cholesterol is metabolized in the lysosome, which is also the site of mTORC1 activation, owing to the tethering of RAG GTPases, which regulate mTORC1 activity, to lysosomes. The authors found that an increase in lysosomal cholesterol level stimulated mTORC1 signalling, whereas cholesterol depletion suppressed it. The lysosomal amino acid transporter SLC38A9 was then found to also bind to cholesterol and to translate high cholesterol levels to mTORC1 activation through the regulation of RAG GTPase activity. Finally, the cholesterol-mediated mTORC1 activation was demonstrated to be negatively regulated by the cholesterol transporter NPC1, which is involved in cholesterol export from lysosomes.
References
Castellano, B. M. et al. Lysosomal cholesterol activates mTORC1 via an SLC38A9-Niemann–Pick C1 signaling complex. Science http://dx.doi.org/10.1126/science.aag1417 355, 1306–1311 (2017)
Rights and permissions
About this article
Cite this article
Strzyz, P. Cholesterol feeds into cell growth control. Nat Rev Mol Cell Biol 18, 277 (2017). https://doi.org/10.1038/nrm.2017.41
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrm.2017.41