《生命科学》 2023, 35(7): 947-955

溶酶体阳离子通道的生理、病理功能研究进展

杨传艳^1,2 , 于　烨^1,* , 高召兵^2,* , 李　平^2,*

¹中国药科大学基础医学与临床药学学院，南京 210009 ²中科中山药物创新研究院，中山 528400

摘　要：

溶酶体(lysosome) 是细胞内重要的细胞器，参与细胞代谢、迁移、死亡等过程。溶酶体上表达的多种离子通道(ion channel) 是溶酶体生理功能的基本保障，它们对维持溶酶体pH 稳态、钙离子稳态、膜电位、融合、分裂、外泌及重新生成等过程具有非常重要的作用。溶酶体离子通道参与多种疾病的发生发展过程，并被认为是某些疾病药物治疗的潜在新靶点。本文总结了溶酶体上五种阳离子通道(TRPML1、TPC、TMEM175、BK、P2X4) 的生理、病理功能的研究进展，并探讨后续靶向这些溶酶体离子通道的药物研发的可行性。

通讯作者：于　烨 , Email:yuye@cpu.edu.cn 高召兵 , Email:bgao@ simm.ac.cn 李　平 , Email:lipingt@simm.ac.cn

Advances in the physiological and pathological functions of lysosomal cation channels

YANG Chuan-Yan^1,2 , YU Ye^1,* , GAO Zhao-Bing^2,* , LI Ping^2,*

¹School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China ²Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China

Abstract:

Lysosome is one of the important organelles in cells, which participates in various biological processes, including cell metabolism, migration, and death. Recently, lysosome has been found equipped with lysosome ion channels that play fundamental roles in maintaining lysosome physiologies. Lysosome ion channels are critical for a variety of characteristics of the lysosome, such as lysosomal pH, calcium homeostasis, membrane potential, fusion, fission, exocytosis, biogenesis, and so on. The deficiency of lysosome ion channels is usually related to a series of human diseases. They are exhibiting potential in drug development. Herein, we summarize the channel properties, and physiological and pathological functions of the five cation channels, TRPML1, TPC, TMEM175, BK, P2X4, on lysosomes, and discuss the feasibility of drug development targeting these channels.

Communication Author：YU Ye , Email:yuye@cpu.edu.cn GAO Zhao-Bing , Email:bgao@ simm.ac.cn LI Ping , Email:lipingt@simm.ac.cn