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

肝脏是重要的代谢和解毒器官，受到多种内源性或外源性损伤。肝细胞线粒体经历各种结构和功能缺陷，包括肝损伤、承受氧化应激、代谢失调和线粒体质量控制 (MQC) 机制的紊乱。线粒体功能障碍启动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形成加重肝损伤和疾病进展。消除线粒体损伤或改善 MQC 机制可恢复线粒体稳态并有益于肝脏健康。这篇综述讨论了线粒体疾病与肝脏病理生理过程的关系以及由此产生的线粒体靶向治疗肝脏疾病的潜力。MQC 机制和线粒体衍生的损伤相关分子模式 (DAMP) 在肝病的病理学和治疗中的最新进展尤其受到关注。