Shi Shaojun, Wang Ling, van der Laan Luc J W, Pan Qiuwei, Verstegen Monique M A
Department of Surgery, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
Transplantation. 2021 Nov 1;105(11):2362-2373. doi: 10.1097/TP.0000000000003691.
Mitochondria are essential organelles for cellular energy and metabolism. Like with any organ, the liver highly depends on the function of these cellular powerhouses. Hepatotoxic insults often lead to an impairment of mitochondrial activity and an increase in oxidative stress, thereby compromising the metabolic and synthetic functions. Mitochondria play a critical role in ATP synthesis and the production or scavenging of free radicals. Mitochondria orchestrate many cellular signaling pathways involved in the regulation of cell death, metabolism, cell division, and progenitor cell differentiation. Mitochondrial dysfunction and oxidative stress are closely associated with ischemia-reperfusion injury during organ transplantation and with different liver diseases, including cholestasis, steatosis, viral hepatitis, and drug-induced liver injury. To develop novel mitochondria-targeting therapies or interventions, a better understanding of mitochondrial dysfunction and oxidative stress in hepatic pathogenesis is very much needed. Therapies targeting mitochondria impairment and oxidative imbalance in liver diseases have been extensively studied in preclinical and clinical research. In this review, we provide an overview of how oxidative stress and mitochondrial dysfunction affect liver diseases and liver transplantation. Furthermore, we summarize recent developments of antioxidant and mitochondria-targeted interventions.
线粒体是细胞能量和代谢的重要细胞器。与任何器官一样，肝脏高度依赖这些细胞动力源的功能。肝毒性损伤常导致线粒体活性受损和氧化应激增加，从而损害代谢和合成功能。线粒体在ATP合成以及自由基的产生或清除中起关键作用。线粒体协调许多参与细胞死亡、代谢、细胞分裂和祖细胞分化调节的细胞信号通路。线粒体功能障碍和氧化应激与器官移植期间的缺血再灌注损伤以及包括胆汁淤积、脂肪变性、病毒性肝炎和药物性肝损伤在内的不同肝脏疾病密切相关。为了开发新的线粒体靶向治疗方法或干预措施，非常需要更好地了解肝脏发病机制中的线粒体功能障碍和氧化应激。针对肝脏疾病中线粒体损伤和氧化失衡的治疗方法已在临床前和临床研究中得到广泛研究。在这篇综述中，我们概述了氧化应激和线粒体功能障碍如何影响肝脏疾病和肝移植。此外，我们总结了抗氧化剂和线粒体靶向干预措施的最新进展。
