WDR83/MORG1 inhibits RRAG GTPase-MTORC1 signaling to facilitate basal autophagy
Permanent lenke
https://hdl.handle.net/10037/35241Dato
2024-03-07Type
Journal articleTidsskriftartikkel
Peer reviewed
Sammendrag
Macroautophagy/autophagy is a conserved lysosomal degradation process composed of both selective and nonselective degradation pathways. The latter occurs upon nutrient depletion. Selective
autophagy exerts quality control of damaged organelles and macromolecules and is going on also
under nutrient-replete conditions. Proper regulation of autophagy is vital for cellular homeostasis
and prevention of disease. During nutrient availability, autophagy is inhibited by the MTORC1
signaling pathway. However, selective, basal autophagy occurs continuously. How the MTORC1
pathway is fine-tuned to facilitate basal constitutive autophagy is unclear. Recently, we identified
the WD-domain repeat protein WDR83/MORG1 as a negative regulator of MTORC1 signaling allowing
basal, selective autophagy. WDR83 interacts with both the Ragulator and active RRAG GTPases to
prevent recruitment of the MTORC1 complex to the lysosome. Consequently, WDR83 depletion leads
to hyperactivation of the MTORC1 pathway and a strong decrease in basal autophagy. As
a consequence of WDR83 depletion cell proliferation and migration increase and low levels of
WDR83 mRNA are correlated with poor prognosis for several cancers.
Forlag
Taylor & FrancisSitering
Kournoutis, Lamark, Johansen, Abudu. WDR83/MORG1 inhibits RRAG GTPase-MTORC1 signaling to facilitate basal autophagy. Autophagy. 2024Metadata
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Copyright 2024 The Author(s)