title: Advances and New Concepts in Alcohol-Induced Organelle Stress, Unfolded Protein Responses and Organ Damage.
abstract: Alcohol is a simple and consumable biomolecule yet its excessive consumption disturbs numerous biological pathways damaging nearly all organs of the human body. One of the essential biological processes affected by the harmful effects of alcohol is proteostasis, which regulates the balance between biogenesis and turnover of proteins within and outside the cell. A significant amount of published evidence indicates that alcohol and its metabolites directly or indirectly interfere with protein homeostasis in the endoplasmic reticulum (ER) causing an accumulation of unfolded or misfolded proteins, which triggers the unfolded protein response (UPR) leading to either restoration of homeostasis or cell death, inflammation and other pathologies under severe and chronic alcohol conditions. The UPR senses the abnormal protein accumulation and activates transcription factors that regulate nuclear transcription of genes related to ER function. Similarly, this kind of protein stress response can occur in other cellular organelles, which is an evolving field of interest. Here, I review recent advances in the alcohol-induced ER stress response as well as discuss new concepts on alcohol-induced mitochondrial, Golgi and lysosomal stress responses and injuries.
authors.affiliation: GI/Liver Division, Research Center for Liver Disease, Department of Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90033, USA. chengji@usc.edu.
authors.forename: Cheng
authors.initials: C
authors.lastname: Ji
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress; D000431:Ethanol / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000378:metabolism* / Q000473:pathology; D008247:Lysosomes / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D056811:Unfolded Protein Response
chemical_list: D000431:Ethanol
keywords: UPR; alcohol; inter-organellar crosstalk; organ injuries; proteostasis stress responses