Topic：Molecular Physiology of Lysosomes

　　Speaker：Prof. Haoxin Xu

　　Time：13:00-14:30，March 23rd 2023

　　Venue：Youcai Deng Lectrue Hall

　　Host：Prof. Liangyi Chen

　　　Abstract

　　More than 50 human diseases collectively called lysosome storage diseases (LSDs) are the result of problems in trafficking to, degradation within, or export from lysosomes. Emerging evidence suggests that common neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are also lysosomal (dysfunction) disorders.  In response to cellular cues in the endocytic and autophagic pathways, lysosomes use H+ flux to establish the working environment for hydrolases, H⁺, Na⁺, K⁺, and Cl^- fluxes to establish the lysosomal membrane potential essential for driving catabolite export, and Ca²⁺ and H⁺ channels to carry the signals needed for precise delivery of cargo and hydrolases, as well as timely removal of catabolites.  

　　Dr. Xu has developed a unique research program for understanding the cell biology of lysosomes, and its relationship to lysosomal storage disorders and common neurodegenerative diseases such as AD and PD. This program combines electrophysiological and imaging approaches typically used to study plasma membrane ion channels with molecular and biochemical approaches typically used to understand organelle function. The combined approach has allowed his lab to find eight lysosomal ion channels (Ca²⁺, Na⁺, K⁺, Fe²⁺/Zn²⁺, Cl^-, and H⁺) and identify the activating cellular cue for each of them. With his unique and combined expertise in both organellar electrophysiology and chemical cell biology, Dr. Xu’s work may not only reveal at the molecular level how information exchange occurs rapidly between the lysosomal lumen and cytosol, but also lead to new therapeutic approaches to treating lysosomal diseases.