医学创新论坛第89期

时间：2025年12月3日（周三）下午16:00

地点：首都医科大学基础科研楼北楼二层多功能厅

主持人：

郭鹏飞

首都医学科学创新中心

报告人：

张宏

教授

中国科学院生物物理研究所

报告题目：

Dynamic Ca²⁺ Signals Drive Autophagosome Formation

报告人简介：

Dr. Hong Zhang is an Investigator at the Institute of Biophysics, Chinese Academy of Sciences. His laboratory pioneered the use of C. elegans as a genetic model to identify a group of metazoan-specific autophagy genes, known as Epg genes. Further work from his team demonstrated that these Epg genes act at steps unique to the autophagy pathway in multicellular organisms. Currently, research in Dr. Zhang’s lab focuses on the role of dynamic Ca²⁺ signaling in various aspects of autophagy. Dr. Zhang serves as an Associate Editor for Autophagy and a Senior Academic Editor for the Journal of Cell Biology. He is also a member of the Editorial Boards of Developmental Cell, Cell Chemical Biology, Trends in Biochemical Sciences, and EMBO Reports.

摘要：

Autophagy, an evolutionarily conserved lysosomal degradation pathway, sustains cellular homeostasis by recycling cytoplasmic material and eliminating cytotoxic threats. The core of this process is the biogenesis of the autophagosome, a double-membraned vesicle that forms through the initiation, expansion, and closure of an isolation membrane. In metazoans, autophagosomes assemble on the endoplasmic reticulum (ER). Pioneering genetic studies in model organisms identified a core autophagy machinery (ATG and EPG genes), and subsequent work revealed that the FIP200 complex—the functional equivalent of the yeast Atg1 complex—translocates to the ER to recruit downstream factors upon autophagy induction. Despite these advances, the fundamental mechanism that initiates the formation of the autophagosome on the ER membrane has remained a central unanswered question in the field.

Our previous research revealed that diverse autophagy stimuli trigger localized Ca²⁺ transients on the outer ER membrane. These ER-localized Ca²⁺ signals trigger the liquid-liquid phase separation of the FIP200 complex. The resultant liquid-like FIP200 condensates associate with the ER, and further mature into functional autophagosome formation sites. In my talk, I will present our recent progress in understanding how these ER Ca²⁺ transients are sustained during autophagy induction and how they are decoded to trigger the assembly of ER-associated FIP200 condensates.

代表性论文：