Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS, 66160, USA.
Harold Hamm Diabetes Center, Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Mol Aspects Med. 2021 Dec;82:100973. doi: 10.1016/j.mam.2021.100973. Epub 2021 Jun 11.
The liver is a highly dynamic metabolic organ that plays critical roles in plasma protein synthesis, gluconeogenesis and glycogen storage, cholesterol metabolism and bile acid synthesis as well as drug/xenobiotic metabolism and detoxification. Research from the past decades indicate that autophagy, the cellular catabolic process mediated by lysosomes, plays an important role in maintaining cellular and metabolic homeostasis in the liver. Hepatic autophagy fluctuates with hormonal cues and the availability of nutrients that respond to fed and fasting states as well as circadian activities. Dysfunction of autophagy in liver parenchymal and non-parenchymal cells can lead to various liver diseases including non-alcoholic fatty liver diseases, alcohol associated liver disease, drug-induced liver injury, cholestasis, viral hepatitis and hepatocellular carcinoma. Therefore, targeting autophagy may be a potential strategy for treating these various liver diseases. In this review, we will discuss the current progress on the understanding of autophagy in liver physiology. We will also discuss several forms of selective autophagy in the liver and the molecular signaling pathways in regulating autophagy of different cell types and their implications in various liver diseases.
肝脏是一个高度动态的代谢器官,在血浆蛋白合成、糖异生和糖原储存、胆固醇代谢和胆汁酸合成以及药物/外源性化合物代谢和解毒等方面发挥着关键作用。过去几十年的研究表明,自噬是溶酶体介导的细胞分解代谢过程,在维持肝脏的细胞和代谢稳态方面起着重要作用。肝自噬随激素信号和营养物质的可用性而波动,这些信号和营养物质对进食和禁食状态以及昼夜节律活动作出反应。肝实质细胞和非实质细胞中自噬功能障碍可导致各种肝脏疾病,包括非酒精性脂肪性肝病、酒精相关性肝病、药物性肝损伤、胆汁淤积、病毒性肝炎和肝细胞癌。因此,靶向自噬可能是治疗这些各种肝脏疾病的一种潜在策略。在这篇综述中,我们将讨论目前对肝脏生理学中自噬的理解的最新进展。我们还将讨论肝脏中的几种选择性自噬形式,以及调节不同细胞类型自噬的分子信号通路及其在各种肝脏疾病中的意义。