Liver autophagy: much more than just taking out the trash

• Published in: Nature reviews. Gastroenterology & hepatology Vol. 11; no. 3; pp. 187 - 200
• Main Authors: Schneider, Jaime L., Cuervo, Ana Maria
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2014; Nature Publishing Group
• Subjects: 692/699/1503/1607/2750; 692/699/1503/234/2513; 692/699/317; 692/699/67/1504/1610; Autophagy; Autophagy (Cytology); Biomedicine; Carcinogenesis; Gastroenterology; Hepatocytes; Hepatocytes - pathology; Hepatology; Homeostasis; Humans; Liver; Liver - pathology; Liver diseases; Liver Diseases - pathology; Lysosomes; Lysosomes - pathology; Medicine & Public Health; Nutritional status; Organelles; Phagocytosis; Physiological aspects; Physiological research; review-article
• ISSN: 1759-5045; 1759-5053
• DOI: 10.1038/nrgastro.2013.211

Key Points Autophagy contributes to the maintenance of the energetic balance, participates in hepatocyte quality control and aids in the defence against exogenous pathogens and conditions that cause cellular toxicity in the liver The different autophagic pathways that coexist in the liver are in dynamic intercommunication with one another, enabling a coordinated response to maintain homeostasis Failure to properly execute the autophagic program leaves hepatocytes vulnerable to stressors and unable to accommodate the extreme energetic demands of this organ Autophagy malfunction underlies the pathogenesis of common liver diseases, including metabolic disorders, protein conformational diseases, viral infection and carcinogenesis Chemical modulation of autophagy has proven to be beneficial in certain liver pathologies, although manipulation of autophagy needs to be customized according to the status of the autophagic pathway in each disease state In this Review—intended as an introduction to the topic of hepatic autophagy for clinical scientists—the authors 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. 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.