Show simple item record

dc.contributor.authorAbudu, Yakubu Princely
dc.contributor.authorKournoutis, Athanasios
dc.contributor.authorBrenne, Hanne Britt
dc.contributor.authorLamark, Trond
dc.contributor.authorJohansen, Terje
dc.date.accessioned2024-10-10T08:23:15Z
dc.date.available2024-10-10T08:23:15Z
dc.date.issued2023-12-15
dc.description.abstractAutophagy, an important quality control and recycling process vital for cellular homeostasis, is tightly regulated. The mTORC1 signaling pathway regulates autophagy under conditions of nutrient availability and scarcity. However, how mTORC1 activity is fine-tuned during nutrient availability to allow basal autophagy is unclear. Here, we report that the WD-domain repeat protein MORG1 facilitates basal constitutive autophagy by inhibiting mTORC1 signaling through Rag GTPases. Mechanistically, MORG1 interacts with active Rag GTPase complex inhibiting the Rag GTPase-mediated recruitment of mTORC1 to the lysosome. MORG1 depletion in HeLa cells increases mTORC1 activity and decreases autophagy. The autophagy receptor p62/SQSTM1 binds to MORG1, but MORG1 is not an autophagy substrate. However, p62/SQSTM1 binding to MORG1 upon re-addition of amino acids following amino acid’s depletion precludes MORG1 from inhibiting the Rag GTPases, allowing mTORC1 activation. MORG1 depletion increases cell proliferation and migration. Low expression of MORG1 correlates with poor survival in several important cancers.en_US
dc.identifier.citationAbudu, Kournoutis, Brenne, Lamark, Johansen. MORG1 limits mTORC1 signaling by inhibiting Rag GTPases. Molecular Cell. 2024;84(3):552-569.e11en_US
dc.identifier.cristinIDFRIDAID 2246260
dc.identifier.doi10.1016/j.molcel.2023.11.023
dc.identifier.issn1097-2765
dc.identifier.issn1097-4164
dc.identifier.urihttps://hdl.handle.net/10037/35168
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalMolecular Cell
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2024 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleMORG1 limits mTORC1 signaling by inhibiting Rag GTPasesen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


File(s) in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)