The Role of Autophagy in Alcohol-Induced Liver Injury

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DESCRIPTION (provided by applicant): Alcohol abuse and consumption are major causes of liver disease and is a major health problem in the United States. The characteristics of this disease are fatty liver, hepatitis, fibrosis, and cirrhosis. Cirrhosis is the eleventh leading cause of death in the United States. Alcohol abuse and alcoholism accounts for approximately 50 % of all death induced by liver cirrhosis. However, the pathogenesis of alcoholic liver diseases (ALD) is not completely understood although recent researches suggest that oxidative stress- induced mitochondrial damage and apoptosis are involved in the development of ALD. It is estimated that 28% of the adult population has a high-risk drinking pattern, such as binge drinking (1). Although there are large number of studies regarding the hepatotoxicity due to excessive drinking, the effects of drinking too much and too fast (binge drinking) on the liver have been sparingly studied. Autophagy is a genetically programmed, evolutionarily conserved process that degrades long-lived cellular proteins and damaged organelles including mitochondria. Whether ethanol can induce autophagy, or whether autophagy plays a role in alcohol-induced liver pathogenesis is not known. We have obtained evidence that ethanol treatment of hepatocytes can lead to the accumulation of autophagosomes. We hypothesize that ethanol can induce autophagy which is important for the removal of damaged mitochondria caused by ethanol; and that autophagy can modulate ethanol-induced cell death. It is anticipated that this work will generate novel finding regarding the role of autophagy in alcoholic pathogenesis. Public Health Relevance: Alcohol abuse and consumption are major causes of liver disease and is a major health problem in the United States. Autophagy has been shown to be able to regulate cell death and organelle turn over including mitochondria, which is an important mechanism in alcoholic liver disease. Elucidating the molecular mechanisms of how autophagy and cell death are integrated in alcoholic liver disease will help to generate novel therapeutic strategies.