《生命科学》 2026, 38(7): 1314-1323

氯离子细胞内通道蛋白1的功能及其在疾病中的研究 进展

王 娜^1,2 , 宋阳冉² , 窦雪儿^1,2 , 李慧霞^1,2,* , 冯若飞^1,2,*

¹西北民族大学生物医学研究中心，生物工程与技术国家民委重点实验室，兰州 730030 ²西北民族大学生物工程学院，兰州 730030

摘　要：

氯离子细胞内通道蛋白1（chloride intracellular channel protein 1，CLIC1）是一类广泛分布于哺乳动物细胞 胞质及多种细胞器质膜上的氧化还原敏感型通道蛋白，主要以可溶性和膜结合两种形式存在。作为细胞氧化应激 响应中关键的感受器与效应器，CLIC1是多种疾病的潜在生物标志物或治疗靶点，具有良好的应用潜力。基于此，本 文系统概述了CLIC1的结构特征、可溶性与膜结合形式的转换特性及其作为氧化应激感受器和离子通道蛋白的核心 功能，聚焦于CLIC1对ERK/MAPK、Nrf2/HO-1及PI3K/Akt/mTOR等信号通路的调控，系统梳理了该蛋白在肿瘤、神 经系统疾病、炎症及病毒感染中发挥关键作用的分子机制研究进展，希望为CLIC1相关疾病的机制解析、生物标志物 筛选及靶向治疗策略开发奠定理论基础。

通讯作者：李慧霞 , Email:lihui.xia@163.com 冯若飞 , Email:fengruofei@xbmu.edu.cn

Research progress on chloride intracellular channel protein 1 in diseases

WANG Na^1,2 , SONG Yang-Ran² , DOU Xue-Er^1,2 , LI Hui-Xia^1,2,* , FENG Ruo-Fei^1,2,*

¹Key Laboratory of Biotechnology and Engineering of State Ethnic Affairs Commission, Biomedical Research Center, Northwest Minzu University, Lanzhou 730030, China ²School of Bioengineering, Northwest Minzu University, Lanzhou 730030, China

Abstract:

Chloride intracellular channel protein 1 (CLIC1) is a redox-sensitive metamorphic protein widely distributed in the cytoplasm and membranes of various organelles in mammalian cells. It exists in two interconvertible forms—soluble and membrane-bound—and functions as a key sensor and effector in cellular oxidative stress responses. This review systematically summarizes the structural characteristics of CLIC1, the molecular mechanisms governing its soluble-to- membrane form conversion, and the regulatory factors influencing its membrane localization, including pH, cholesterol, zinc ions, and temperature. We comprehensively discuss the dual biochemical activities of CLIC1—glutathione S-transferase (GST)-like enzymatic activity and chloride ion channel activity—and their functional coupling. Accumulating evidence has established CLIC1 as a critical regulator of multiple signaling pathways, including ERK/MAPK, Nrf2/HO-1, and PI3K/Akt/ mTOR, thereby contributing to the pathogenesis of various diseases. In oncology, CLIC1 promotes tumor cell proliferation, migration, invasion, and metabolic reprogramming while also modulating chemotherapy resistance. In neurological disorders, CLIC1 drives neuroinflammation by activating microglial NLRP3 inflammasome and serves as a potential biomarker for Alzheimer’s disease and multiple sclerosis. In vascular diseases, CLIC1 mediates endothelial dysfunction, atherosclerosis, and thrombosis. Furthermore, CLIC1 functions as a key host factor in viral replication, participating in different stages of the viral life cycle for Chikungunya virus, influenza A virus, and porcine reproductive and respiratory syndrome virus. The pleiotropic roles of CLIC1 across diverse pathological conditions highlight its potential as a diagnostic biomarker and therapeutic target. Future research should focus on elucidating the tissue-specific regulatory networks of CLIC1 and developing highly selective inhibitors for precision treatment of CLIC1-associated diseases.

Communication Author：LI Hui-Xia , Email:lihui.xia@163.com FENG Ruo-Fei , Email:fengruofei@xbmu.edu.cn