线粒体相关内质网膜在非酒精性脂肪肝病中的作用及研究进展

Role of mitochondria-associated endoplasmic reticulum membranes in pathogenesis of non-alcoholic fatty liver disease

摘要:

非酒精性脂肪性肝病（NAFLD）是全球发病率最高的慢性肝病，包括肝脏脂肪变性、非酒精性脂肪性肝炎、肝硬化、肝细胞癌。线粒体相关内质网膜（MAM）是线粒体与内质网密切接触的部位，在钙稳态、线粒体稳态、细胞凋亡、自噬、脂代谢等细胞生理功能调控中发挥着重要作用。这些细胞功能深度参与了NAFLD的发生、发展，在肝细胞脂质沉积、炎症反应、凋亡、纤维化等过程中发挥关键作用。因此MAM越来越成为NAFLD的潜在治疗靶点。该文就MAM及其调控的细胞功能在NAFLD发生、发展中的作用进行了综述。

Abstract:

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Its disease spectrum ranges from liver steatosis to non-alcoholic steatohepatitis, which may ultimately progress to liver cirrhosis and hepatocellular carcinoma. Mitochondria-associated endoplasmic reticulum membranes (MAMs) are structures where the mitochondria and the endoplasmic reticulum (ER) are in close contact, and play vital roles in different cellular processes, such as calcium homeostasis, mitochondrial homeostasis, apoptosis, autophagy, and lipid metabolism. These processes are deeply involved in the onset and progression of NAFLD, and are crucial in multiple processes in hepatocytes including lipid accumulation, inflammation, apoptosis and fibrosis. Therefore, MAMs are increasingly emerging as a potential therapeutic target for NAFLD. In this review, we summarized the roles of MAMs and cellular functions regulated by MAMs in the pathogenesis of NAFLD.