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线粒体钙单向转运体复合物在代谢相关脂肪性肝病中的作用机制
DOI: 10.12449/JCH260831
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：张鑫宇负责查阅文献，撰写论文；淡丽娟、游晓洁负责分析资料，修改论文；宋虹霏、穆杰负责拟定写作思路，指导撰写文章并最后定稿。
Mechanism of action of mitochondrial calcium uniporter complex in treatment of metabolic dysfunction-associated fatty liver disease
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摘要: 代谢相关脂肪性肝病（MAFLD）是一种与脂质代谢失调密切相关的慢性肝病，其核心病理环节是肝细胞线粒体功能障碍。线粒体钙单向转运体（MCU）复合物是调控线粒体钙（mtCa2+）稳态的关键结构，其功能紊乱所致的mtCa2+超载在MAFLD进展中发挥关键作用。本文系统论述了MAFLD的发病机制，并重点阐释了“MCU复合物功能障碍-mtCa2+超载”这一核心信号如何通过干扰能量代谢、激活腺苷一磷酸活化的蛋白质激酶信号通路、触发核苷酸结合寡聚结构域样受体家族热蛋白结构域相关蛋白3炎症小体及诱导细胞死亡，从而驱动MAFLD的疾病进程。同时指出，中医药能够多靶点干预下游多个通路，在靶向MCU复合物以维持线粒体稳态从而改善MAFLD中展示出独特优势与极大潜力，有望为MAFLD的防治开辟新途径。Abstract: Metabolic dysfunction-associated fatty liver disease （MAFLD） is a chronic liver condition closely associated with dysregulated lipid metabolism， with the central pathological event of mitochondrial dysfunction in hepatocytes. The mitochondrial calcium uniporter （MCU） complex is a key molecular apparatus regulating mitochondrial calcium （mtCa2+） homeostasis， and mtCa2+ overload due to its dysfunction plays a critical role in the progression of MAFLD. This article systematically elaborates on the pathogenesis of MAFLD， with a particular focus on how the central signaling axis of “MCU complex dysfunction-mtCa2+ overload” drives the disease progression of MAFLD by disrupting energy metabolism， activating the adenosine monophosphate-activated protein kinase signaling pathway， triggering the NOD-like receptor protein 3 inflammasome， and inducing cell death. It also points out that traditional Chinese medicine can exert an interventional effect on multiple downstream pathways through various targets and has shown unique advantages and a significant potential in alleviating MAFLD by maintaining mitochondrial homeostasis and targeting the MCU complex， and therefore， it is expected to provide new strategies for the prevention and treatment of MAFLD.
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