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肝脏疾病中的线粒体功能障碍与靶向线粒体治疗策略。

Mitochondrial dysfunction and mitochondrion-targeted therapeutics in liver diseases.

机构信息

School of Chemistry and Chemical Engineering, University of South China, Hengyang, China.

Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang, China.

出版信息

J Drug Target. 2021 Dec;29(10):1080-1093. doi: 10.1080/1061186X.2021.1909051. Epub 2021 Apr 9.

Abstract

The liver is a vital metabolic and detoxifying organ and suffers diverse endogenous or exogenous damage. Hepatocyte mitochondria experience various structural and functional defects from liver injury, bearing oxidative stress, metabolic dysregulation, and the disturbance of mitochondrial quality control (MQC) mechanisms. Mitochondrial malfunction initiates the mitochondria-mediated apoptotic pathways and the release of damage signals, aggravating liver damage and disease progression via inflammation and reparative fibrogenesis. Removal of mitochondrial impairment or the improvement of MQC mechanisms restore mitochondrial homeostasis and benefit liver health. This review discusses the association of mitochondrial disorders with hepatic pathophysiological processes and the resultant potential of mitochondrion-targeting therapeutics for hepatic disorders. The recent advances in the MQC mechanisms and the mitochondrial-derived damage-associated molecular patterns (DAMPs) in the pathology and treatment of liver disease are particularly focussed.

摘要

肝脏是一个重要的代谢和解毒器官,容易受到各种内源性或外源性损伤。肝损伤可导致肝细胞线粒体出现各种结构和功能缺陷,承受氧化应激、代谢紊乱和线粒体质量控制(MQC)机制的破坏。线粒体功能障碍会引发线粒体介导的凋亡途径和损伤信号的释放,通过炎症和修复性纤维发生加重肝损伤和疾病进展。消除线粒体损伤或改善 MQC 机制可恢复线粒体的稳态,有益于肝脏健康。本综述讨论了线粒体功能障碍与肝生理病理过程的关系,以及针对肝脏疾病的靶向线粒体治疗的潜在可能。特别关注了 MQC 机制的最新进展以及线粒体来源的损伤相关分子模式(DAMPs)在肝病发病机制和治疗中的作用。

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