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This study aims to explore the effects of quercetin on ferroptosis in ALD and elucidates the underlying mechanism involving the formation of mitochondria\u2010associated endoplasmic reticulum membranes (MAMs) mediated by protein kinase RNA\u2010like endoplasmic reticulum kinase (PERK).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      C57BL\/6J mice are fed either a regular or an ethanol\u2010containing liquid diet (with 28% energy form ethanol) with or without quercetin supplementation (100\u00a0mg\u00a0kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      BW) for 12 weeks. Ethanol feeding or treatment induced ferroptosis in mice and AML12 cells, which is associated with increased MAMs formation and PERK expression within MAMs. Quercetin attenuates these changes and protects against ethanol\u2010induced liver injury. The antiferroptotic effect of quercetin is abolished by ferroptosis inducers, but mimicked by ferroptosis inhibitors and PERK knockdown. The study demonstrates that PERK structure, rather than its kinase activity (transfected with the K618A site mutation that inhibits kinase activity\u2010\u0394K plasmid or protein C terminal knockout\u2010\u0394C plasmid of PERK), mediates the enhanced MAMs formation and ferroptosis during the ethanol exposure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Quercetin ameliorates ethanol\u2010induced liver injury by inhibiting ferroptosis via modulating PERK\u2010dependent MAMs formation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mnfr.202300343","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T08:48:15Z","timestamp":1710838095000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Ethanol\u2010Induced Hepatic Ferroptosis Is Mediated by PERK\u2010Dependent MAMs Formation: Preventive Role of Quercetin"],"prefix":"10.1002","volume":"68","author":[{"given":"Hongkun","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene School of Public Health\uff0cTongji Medical College Huazhong University of Science &amp; Technology  13 Hangkong Road Wuhan 430030 P. 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