MORG1 limits mTORC1 signaling by inhibiting Rag GTPases
Permanent lenke
https://hdl.handle.net/10037/35168Dato
2023-12-15Type
Journal articleTidsskriftartikkel
Peer reviewed
Forfatter
Abudu, Yakubu Princely; Kournoutis, Athanasios; Brenne, Hanne Britt; Lamark, Trond; Johansen, TerjeSammendrag
Autophagy, 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.
Forlag
ElsevierSitering
Abudu, Kournoutis, Brenne, Lamark, Johansen. MORG1 limits mTORC1 signaling by inhibiting Rag GTPases. Molecular Cell. 2024;84(3):552-569.e11Metadata
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