自噬
TFEB
溶酶体
mTORC1型
细胞生物学
雷帕霉素的作用靶点
生物
自噬体
PI3K/AKT/mTOR通路
mTORC2型
液泡
内体
ULK1
细胞器
吞噬体
ATG16L1
生物化学
信号转导
细胞凋亡
酶
作者
Jing Zhou,Siew‐Ann Tan,Valérie Nicolas,Chantal Bauvy,Naidi Yang,Jianbin Zhang,Yuan Xue,Patrice Codogno,Han‐Ming Shen
出处
期刊:Cell Research
[Springer Nature]
日期:2013-01-22
卷期号:23 (4): 508-523
被引量:327
摘要
Lysosome is a key subcellular organelle in the execution of the autophagic process and at present little is known whether lysosomal function is controlled in the process of autophagy. In this study, we first found that suppression of mammalian target of rapamycin (mTOR) activity by starvation or two mTOR catalytic inhibitors (PP242 and Torin1), but not by an allosteric inhibitor (rapamycin), leads to activation of lysosomal function. Second, we provided evidence that activation of lysosomal function is associated with the suppression of mTOR complex 1 (mTORC1), but not mTORC2, and the mTORC1 localization to lysosomes is not directly correlated to its regulatory role in lysosomal function. Third, we examined the involvement of transcription factor EB (TFEB) and demonstrated that TFEB activation following mTORC1 suppression is necessary but not sufficient for lysosomal activation. Finally, Atg5 or Atg7 deletion or blockage of the autophagosome-lysosome fusion process effectively diminished lysosomal activation, suggesting that lysosomal activation occurring in the course of autophagy is dependent on autophagosome-lysosome fusion. Taken together, this study demonstrates that in the course of autophagy, lysosomal function is upregulated via a dual mechanism involving mTORC1 suppression and autophagosome-lysosome fusion.
科研通智能强力驱动
Strongly Powered by AbleSci AI