Chronic ethanol administration impairs ATP-dependent acidification of endosomes in rat liver

Ethanol administration has been shown to alter various protein trafficking pathways in the liver, including protein secretion, plasma membrane assembly and receptor-mediated endocytosis. Molecules such as proteins are transported into and within the cells via endosomal vesicles, and acidification of these endosomes appears to be critical for efficient sorting and trafficking of proteins. In the present study we examined whether ethanol administration impaired the ATP-dependent acidification of endosomes. Liver endosomes were prepared from rats after intravenous labeling with fluorescently labeled ligands and the initial pH and extent of ATP-dependent acidification was determined. Our results showed that the intrinsic pH was significantly higher and that the ATP-dependent acidification of the interior of the endosomes was inhibited in ethanol-fed versus control animals. This impairment of endosomal acidification may play a role in the impaired protein trafficking which occurs as a result of ethanol administration.