生物
自噬
mTORC1型
细胞生物学
溶酶体
营养感应
袋3
GTP酶
TFEB
信号转导
调节器
自噬体
PI3K/AKT/mTOR通路
生物化学
细胞凋亡
酶
基因
作者
Athanasios Kournoutis,Trond Lamark,Terje Johansen,Yakubu Princely Abudu
出处
期刊:Autophagy
[Informa]
日期:2024-03-07
卷期号:: 1-2
标识
DOI:10.1080/15548627.2024.2322457
摘要
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.
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