Title:Autophagy: Breaking apart and Putting Together the Massive Recycling Machinery in the Cell Presenter: Associate Prof. Qing Zhong
University:The University of Texas Southwestern Medical Center at Dallas
Time:16:30-17:30, April 22, 2016
Venue: Room A102, Institute of Microbiology, Chinese Academy of Sciences
Abstract: Within a cell, the bulky organelles, protein aggregates and invading pathogens are engulfed in a huge membrane vesicle called autophagosome (“self-eating”) and delivered to lysosomes for degradation and processing. Dysfunction of autophagy has been implicated in a broad spectrum of human diseases. As a membrane vesicle, autophagosome is unique in many aspects compared to other known transporting membrane vesicles, including no protein coat, double membrane, and lack of transmembrane proteins etc., making it difficult to speculate the mechanism underlying its initiation, cargo recruitment, membrane curvature formation, vesicle sealing and membrane fusion to lysosome. Our long term goal is to understand each step of this process and hopefully reconstitute biochemically the autophagy machinery. This knowledge should help us to design chemical or biological tools to control this process and treat human diseases. Although no doubt there will be a long journey, we have some interesting discoveries along the road. We have gained mechanistic insight into the molecular machinery controlling the PI3P production on autophagosome membrane, which is considered the rate-limiting initiating signal for autophagosome biogenesis. We have also reconstituted the minimum fusion machinery for autophagosome fusion with lysosomes. Last but not the least, we have linked autophagy to primary cilia formation; a process might contribute to tumorigenesis in an unexpected way. We are happy about these progresses but understand it is still far away from our final goal. I will also go through what challenges we are currently facing and how we plan to deal with them.