报告题目：Regulation of Lysosomal Function in the Course of Autophagy
主讲人： Han-Ming SHEN, Ph.D.
Associate Professor
Yong Loo Lin School of Medicine, National University of Singapore
Yong Loo Lin School of Medicine, National University of Singapore
主持人： 佟 超 教 授
时 间： 2012年3月31日（星期六）下午14:00
地 点： 医学院综合楼205报告厅
讲座简介：
Autophagy is an evolutionarily conserved catabolic process by which intracellular proteins and organelles are delivered by autophagosomes to lysosomes for degradation. Lysosome is the key subcellular organelle in execution of the autophagic process and at present little is known how lysosomal function is controlled in the course of autophagy. The ongoing work in our lab has examined (i) changes of the lysosomal function in the course of autophagy; and (ii) the involvement of mammalian target of rapamycin (mTOR) in lysosomal activation. We first found that suppr-ession of mTOR activity by starvation or mTOR catalytic inhibitors (PP242 and Torin1), but not by an allosteric inhibitor (rapamycin), leads to activation of lysosomal function in the course of autophagy, indicating a negative regulatory effect of mTOR on lysosomal function . Next, we pro-vided evidence that lysosomal activation is dependent on the autophagosome-lysosome fusion process. Third, we found that it is the rapamycin-insensitive function of mTORC1, but not mTORC2, which is implicated in the inhibitory effect on lysosomal function. Finally, we established the role of TFEB downstream of mTORC1 in lysosomal activation. Taken together, results from this study, for the first time, establish that mTOR has a dual inhibitory effect on autophagy: (i) inhibition on the initiation of autophagy via suppression of ULK1 complex, and (ii) inhibition on the maturation/degradation stage of autophagy by suppression of lysosomal function.
