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World J Gastroenterol. Mar 14, 2009; 15(10): 1178-1185
Published online Mar 14, 2009. doi: 10.3748/wjg.15.1178
Autophagy and ethanol-induced liver injury
Terrence M Donohue Jr
Terrence M Donohue Jr, Liver Study Unit, The Omaha Veterans Affairs Medical Center, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68105, United States
Author contributions: Donohue TM Jr contributed all to this review.
Correspondence to: Terrence M Donohue Jr, PhD, Liver Study Unit, Research Service (151), VA Medical Center, 4101 Woolworth Ave, Omaha, NE 68105, United States. tdonohue@unmc.edu
Telephone: +1-402-9953556
Fax: +1-402-4490604
Received: December 18, 2008
Revised: February 11, 2009
Accepted: February 18, 2009
Published online: March 14, 2009
Abstract

The majority of ethanol metabolism occurs in the liver. Consequently, this organ sustains the greatest damage from ethanol abuse. Ethanol consumption disturbs the delicate balance of protein homeostasis in the liver, causing intracellular protein accumulation due to a disruption of hepatic protein catabolism. Evidence indicates that ethanol or its metabolism impairs trafficking events in the liver, including the process of macroautophagy, which is the engulfment and degradation of cytoplasmic constituents by the lysosomal system. Autophagy is an essential, ongoing cellular process that is highly regulated by nutrients, endocrine factors and signaling pathways. A great number of the genes and gene products that govern the autophagic response have been characterized and the major metabolic and signaling pathways that activate or suppress autophagy have been identified. This review describes the process of autophagy, its regulation and the possible mechanisms by which ethanol disrupts the process of autophagic degradation. The implications of autophagic suppression are discussed in relation to the pathogenesis of alcohol-induced liver injury.

Keywords: Autophagy, Autophagosome, Ethanol metabolism, Hepatomegaly, Lysosomes, Signal transduction