title: Role of mitochondria in alcoholic liver disease.
abstract: Alcohol abuse is the leading cause of liver related morbidity and mortality. Chronic or binge alcohol drinking causes hepatic steatosis which can develop to steatohepatitis, cirrhosis and ultimately hepatocellular carcinoma. The pathogenesis of alcoholic liver disease (ALD) is poorly characterized, however several recent studies point to a major role of mitochondria in this process. Mitochondria play a crucial role in cellular energy metabolism and in reactive species formation. Alcohol treatment causes mitochondrial DNA damage, lipid accumulation and oxidative stress. Studies in both animal models and in humans showed that alcohol administration causes changes in the mitochondrial morphology and function suggesting a role of these changes in the pathogenesis of ALD. We review recent findings on mechanisms by which alcohol negatively impacts mitochondrial biogenesis and function and we will discuss the specific intracellular pathways affected by alcohol consumption. Interestingly, recent findings indicate that a large number of mitochondrial proteins are acetylated and that mitochondrial proteins acetylation and sirtuins are modulated by alcohol. Understanding the mechanisms behind alcohol mediated impaired mitochondrial biogenesis and function may help identify potential therapeutic targets for treating ALD in humans.
authors.affiliation: Fatiha Nassir, Jamal A Ibdah, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Missouri School of Medicine, Columbia, MO 65212, United States.
authors.forename: Fatiha
authors.initials: F
authors.lastname: Nassir
authors.affiliation: Fatiha Nassir, Jamal A Ibdah, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Missouri School of Medicine, Columbia, MO 65212, United States.
authors.forename: Jamal A
authors.initials: JA
authors.lastname: Ibdah
mesh_terms: D000818:Animals; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000378:metabolism; D000431:Ethanol / Q000009:adverse effects* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D012307:Risk Factors
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D000431:Ethanol
keywords: Alcohol; Alcoholic liver disease; Liver; Mitochondria; Sirtuins