title: Selective taste of ethanol-induced autophagy for mitochondria and lipid droplets.
abstract: Alcoholic beverages are one of the most popular drinks in the world, but ethanol can induce significant liver pathology. We have found that ethanol treatment results in autophagy activation, which is at least in part due to the inhibition of mTOR signaling by reactive oxygen species. Autophagy is important in limiting liver injury and hepatocyte apoptosis by removing damaged mitochondria and accumulated lipid droplets, the two most important culprits of ethanol pathogenesis. The selectivity of ethanol-induced autophagy toward these two targets without affecting other cellular substances, such as long-lived proteins, is remarkably in line with its protective effects. However, we still do not quite understand how this selectivity is determined and how the selection process is accomplished, although evidence from other studies indicates that mitophagy involves distinct molecular steps of mobilization of the autophagy machinery and of preparation of mitochondria for recognition. The avoidance of mistargeting to other cellular components may involve additional mechanisms related to how autophagosomes might form in relation to their targets. Ethanol-induced selective mitophagy and lipophagy thus provides an excellent model to study these events in a pathophysiology-relevant context. Most importantly, the understanding of the mechanisms can bring forward new therapeutic modalities to improve the disease outcome.
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Center, Kansas City, KS, USA.
authors.forename: Wen-Xing
authors.initials: WX
authors.lastname: Ding
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Yin
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D008954:Models, Biological; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D008055:Lipids; D017382:Reactive Oxygen Species; D000431:Ethanol