title: Involvement of autophagy in alcoholic liver injury and hepatitis C pathogenesis.
abstract: This review describes the principal pathways of macroautophagy (i.e. autophagy), microautophagy and chaperone-mediated autophagy as they are currently known to occur in mammalian cells. Because of its crucial role as an accessory digestive organ, the liver has a particularly robust autophagic activity that is sensitive to changes in plasma and dietary components. Ethanol consumption causes major changes in hepatic protein and lipid metabolism and both are regulated by autophagy, which is significantly affected by hepatic ethanol metabolism. Ethanol exposure enhances autophagosome formation in liver cells, but suppresses lysosome function. Excessive ethanol consumption synergizes with hepatitis C virus (HCV) to exacerbate liver injury, as alcohol-consuming HCV patients frequently have a longer course of infection and more severe manifestations of chronic hepatitis than abstinent HCV patients. Alcohol-elicited exacerbation of HCV infection pathogenesis is related to modulation by ethanol metabolism of HCV replication. Additionally, as part of this mechanism, autophagic proteins have been shown to regulate viral (HCV) replication and their intracellular accumulation. Because ethanol induces autophagosome expression, enhanced levels of autophagic proteins may enhance HCV infectivity in liver cells of alcoholics and heavy drinkers.
authors.affiliation: University of Nebraska Medical Center, VA Medical Center, Omaha, NE 68105, United States. nosna@unmc.edu
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Osna
authors.forename: Paul G
authors.initials: PG
authors.lastname: Thomes
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Donohue
mesh_terms: D001343:Autophagy / Q000502:physiology*; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology; D016174:Hepacivirus / Q000472:pathogenicity / Q000502:physiology; D006526:Hepatitis C / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000821:virology; D008108:Liver Diseases, Alcoholic / Q000209:etiology* / Q000503:physiopathology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000431:Ethanol