title: Quercetin Attenuates Chronic Ethanol-Induced Hepatic Mitochondrial Damage through Enhanced Mitophagy.
abstract: Emerging evidence suggested mitophagy activation mitigates ethanol-induced liver injury. However, the effect of ethanol on mitophagy is inconsistent. Importantly, the understanding of mitophagy status after chronic ethanol consumption is limited. This study evaluated the effect of quercetin, a naturally-occurring flavonoid, on chronic ethanol-induced mitochondrial damage focused on mitophagy. An ethanol regime to mice for 15 weeks (accounting for 30% of total calories) led to significant mitochondrial damage as evidenced by changes of the mitochondrial ultrastructure, loss of mitochondrial membrane potential and remodeling of membrane lipid composition, which was greatly attenuated by quercetin (100 mg/kg.bw). Moreover, quercetin blocked chronic ethanol-induced mitophagy suppression as denoted by mitophagosomes-lysosome fusion and mitophagy-related regulator elements, including LC3II, Parkin, p62 and voltage-dependent anion channel 1 (VDAC1), paralleling with increased FoxO3a nuclear translocation. AMP-activated protein kinase (AMPK) and extracellular signal regulated kinase 2 (ERK2), instead of AKT and Sirtuin 1, were involved in quercetin-mediated mitophagy activation. Quercetin alleviated ethanol-elicited mitochondrial damage through enhancing mitophagy, highlighting a promising preventive strategy for alcoholic liver disease.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. yuxiao775@126.com.|Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. yuxiao775@126.com.|Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. yuxiao775@126.com.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. yyx@hust.edu.cn.|Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. yyx@hust.edu.cn.|Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. yyx@hust.edu.cn.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. 13035130764@163.com.|Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. 13035130764@163.com.|Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. 13035130764@163.com.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. ycsjian@163.com.|Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. ycsjian@163.com.|Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. ycsjian@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. liupeiyi85@126.com.|Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. liupeiyi85@126.com.|Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. liupeiyi85@126.com.
authors.forename: Peiyi
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. xiaolin0210@hust.edu.cn.|Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. xiaolin0210@hust.edu.cn.|Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. xiaolin0210@hust.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. tyh043@126.com.|Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. tyh043@126.com.|Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. tyh043@126.com.
authors.forename: Yuhan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. lgliu@mails.tjmu.edu.cn.|Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. lgliu@mails.tjmu.edu.cn.|Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. lgliu@mails.tjmu.edu.cn.
authors.forename: Liegang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. yaoping@mails.tjmu.edu.cn.|Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. yaoping@mails.tjmu.edu.cn.|Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. yaoping@mails.tjmu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Yao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D000431:Ethanol; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy; D008297:Male; D008563:Membrane Lipids / Q000737:chemistry; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D063306:Mitophagy / Q000187:drug effects*; D011794:Quercetin / Q000494:pharmacology*; D056564:Sirtuin 1 / Q000378:metabolism; D050995:Voltage-Dependent Anion Channel 1 / Q000378:metabolism
chemical_list: D000975:Antioxidants; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D008563:Membrane Lipids; C494763:Vdac1 protein, mouse; D000431:Ethanol; D011794:Quercetin; D050995:Voltage-Dependent Anion Channel 1; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D055372:AMP-Activated Protein Kinases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: AMPK; ERK2; FoxO3a; mitochondrial damage; mitophagy; quercetin