Schneider Jaime L, Cuervo Ana Maria
Department of Developmental and Molecular Biology, Institute for Aging Studies, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, NY 10461, USA.
Nat Rev Gastroenterol Hepatol. 2014 Mar;11(3):187-200. doi: 10.1038/nrgastro.2013.211. Epub 2013 Nov 5.
Studies performed in the liver in the 1960s led to the identification of lysosomes and the discovery of autophagy, the process by which intracellular proteins and organelles are degraded in lysosomes. Early studies in hepatocytes also uncovered how nutritional status regulates autophagy and how various circulating hormones modulate the activity of this catabolic process in the liver. The intensive characterization of hepatic autophagy over the years has revealed that lysosome-mediated degradation is important not only for maintaining liver homeostasis in normal physiological conditions, but also for an adequate response of this organ to stressors such as proteotoxicity, metabolic dysregulation, infection and carcinogenesis. Autophagic malfunction has also been implicated in the pathogenesis of common liver diseases, suggesting that chemical manipulation of this process might hold potential therapeutic value. In this Review--intended as an introduction to the topic of hepatic autophagy for clinical scientists--we describe the different types of hepatic autophagy, their role in maintaining homeostasis in a healthy liver and the contribution of autophagic malfunction to liver disease.
20世纪60年代在肝脏中进行的研究促成了溶酶体的鉴定以及自噬的发现，自噬是细胞内蛋白质和细胞器在溶酶体中被降解的过程。早期对肝细胞的研究还揭示了营养状况如何调节自噬，以及各种循环激素如何调节肝脏中这种分解代谢过程的活性。多年来对肝脏自噬的深入研究表明，溶酶体介导的降解不仅对于在正常生理条件下维持肝脏稳态很重要，而且对于该器官对应激源（如蛋白毒性、代谢失调、感染和致癌作用）的充分反应也很重要。自噬功能障碍也与常见肝脏疾病的发病机制有关，这表明对这一过程进行化学调控可能具有潜在的治疗价值。在本综述中——旨在为临床科学家介绍肝脏自噬这一主题——我们描述了肝脏自噬的不同类型、它们在健康肝脏中维持稳态的作用以及自噬功能障碍对肝脏疾病的影响。
