title: Alcohol consumption impairs hepatic protein trafficking: mechanisms and consequences.
abstract: Alcoholic liver disease is a major biomedical health concern in the United States. Despite considerable research efforts aimed at understanding the progression of the disease, the specific mechanisms leading to alcohol-induced damage remain elusive. Numerous proteins are known to have alcohol-induced alterations in their dynamics. Defining these defects in protein trafficking is an active area of research. In general, two trafficking pathways are affected: transport of newly synthesized secretory or membrane glycoproteins from the Golgi to the basolateral membrane and clathrin-mediated endocytosis from the sinusoidal surface. Both impaired secretion and internalization require ethanol metabolism and are likely mediated by acetaldehyde. Although the mechanisms by which ethanol exposure impairs protein trafficking are not fully understood, recent work implicates alcohol-induced modifications on tubulin or components of the clathrin machinery as potential mediators. Furthermore, the physiological ramifications of impaired protein trafficking are not fully understood. In this review, we will list and discuss the proteins whose trafficking patterns are known to be impaired by ethanol exposure. We will then describe what is known about the possible mechanisms leading to impaired protein trafficking and how disrupted protein trafficking alters liver function and may explain clinical features of the alcoholic patient.
authors.affiliation: Department of Biology, The Catholic University of America, 620 Michigan Avenue, NE, Washington, DC, 20064, USA.
authors.forename: Blythe D
authors.initials: BD
authors.lastname: Shepard
authors.forename: David J
authors.initials: DJ
authors.lastname: Fernandez
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Tuma