The Ubiquitin-Proteasome System in Alcohol-Induced Pathology

This chapter discusses the ubiquitin proteasome system in pathological conditions induced by alcohol. The ubiquitin proteasome system is a complex proteolytic pathway that was once considered a minor protein degradative pathway in eukaryotic cells. Past research reveals this system to be a major pathway for the degradation of intracellular proteins, for antigen presentation, and for the destruction of abnormal proteins. Furthermore the involvement of the ubiquitin-proteasome pathway in certain disease pathologies has attracted considerable interest in using this pathway as a therapeutic target. This chapter describes the importance of protein degradation in cellular physiology, with specific focus on the functions and mechanism of the ubiquitin-proteasome pathway. Ethanol consumption significantly affects protein catabolism in the liver. Because this organ sustains greater damage than other organs from heavy drinking, most of the discussion centers on changes in the hepatic ubiquitin-proteasome pathway after heavy alcohol consumption in both clinical and experimental settings. It describes the mechanisms behind the formation of Mallory bodies or alcoholic hyaline, the histological hallmarks of alcohol-induced liver disease.