biostudies-literatureKim YMNIDDK NIH HHSNIA NIH HHSNIGMS NIH HHS207-18https://www.ebi.ac.uk/biostudies/studies/S-EPMC4304967biostudies-literatureUnknown57(2)mTORC1 plays a key role in autophagy as a negative regulator. The currently known targets of mTORC1 in the autophagy pathway mainly function at early stages of autophagosome formation. Here, we identify that mTORC1 inhibits later stages of autophagy by phosphorylating UVRAG. Under nutrient-enriched conditions, mTORC1 binds and phosphorylates UVRAG. The phosphorylation positively regulates the association of UVRAG with RUBICON, thereby enhancing the antagonizing effect of RUBICON on UVRAG-mediated autophagosome maturation. Upon dephosphorylation, UVRAG is released from RUBICON to interact with the HOPS complex, a component for the late endosome and lysosome fusion machinery, and enhances autophagosome and endosome maturation. Consequently, the dephosphorylation of UVRAG facilitates the lysoMolecular cellmTORC1 phosphorylates UVRAG to negatively regulate autophagosome and endosome maturation.PMC4304967GM097057AG039758P30 DK050456R01 GM097057P30-DK050456R21 AG039758Kim YMJung CHKim DHKim EKPark JMSeo MBae SSfalsemTORC1 phosphorylates UVRAG to negatively regulate autophagosome and endosome maturation.mTORC1 plays a key role in autophagy as a negative regulator. The currently known targets of mTORC1 in the autophagy pathway mainly function at early stages of autophagosome formation. Here, we identify that mTORC1 inhibits later stages of autophagy by phosphorylating UVRAG. Under nutrient-enriched conditions, mTORC1 binds and phosphorylates UVRAG. The phosphorylation positively regulates the association of UVRAG with RUBICON, thereby enhancing the antagonizing effect of RUBICON on UVRAG-mediated autophagosome maturation. Upon dephosphorylation, UVRAG is released from RUBICON to interact with the HOPS complex, a component for the late endosome and lysosome fusion machinery, and enhances autophagosome and endosome maturation. Consequently, the dephosphorylation of UVRAG facilitates the lyso2015-01-01T00:00:00Z2015 Jan2026-04-14T19:27:27.855Z2019-03-27T01:44:02ZS-EPMC43049672553318710.1016/j.molcel.2014.11.013