{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:28:52Z","timestamp":1793039332615,"version":"4.5.0"},"reference-count":72,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T00:00:00Z","timestamp":1656374400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T00:00:00Z","timestamp":1656374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004426","name":"Dr. Werner Jackst\u00e4dt-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004426","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Universit\u00e4tsklinikum Schleswig-Holstein - Campus Kiel"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell. Mol. Life Sci."],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ferroptosis, a type of iron-dependent programmed cell death distinct from apoptosis, necroptosis, and other types of cell death, is characterized by lipid peroxidation, reactive oxygen species production, and mitochondrial dysfunction. Accumulating evidence has highlighted vital roles for ferroptosis in multiple diseases, including acute kidney injury. Therefore, ferroptosis has become a major focus for translational research. However, despite its involvement in pathological conditions, there are no pharmacologic inhibitors of ferroptosis in clinical use. In the context of drug repurposing, a strategy for identifying new uses for approved drugs outside the original medical application, we discovered that vitamin K1 is an efficient inhibitor of ferroptosis. Our findings are strengthened by the fact that the vitamin K antagonist phenprocoumon significantly exacerbated ferroptotic cell death in vitro and also massively worsened the course of acute kidney injury in vivo, which is of utmost clinical importance. We therefore assign vitamin K1 a novel role in preventing ferroptotic cell death in acute tubular necrosis during acute kidney injury. Since the safety, tolerability, pharmacokinetics, and pharmacodynamics of vitamin K1 formulations are well documented, this drug is primed for clinical application, and provides a new strategy for pharmacological control of ferroptosis and diseases associated with this mode of cell death.<\/jats:p>","DOI":"10.1007\/s00018-022-04416-w","type":"journal-article","created":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T10:03:01Z","timestamp":1656410581000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Vitamin K1 inhibits ferroptosis and counteracts a detrimental effect of phenprocoumon in experimental acute kidney injury"],"prefix":"10.1007","volume":"79","author":[{"given":"Benedikt","family":"Kolbrink","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich Alexander","family":"von Samson-Himmelstjerna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja Lucia","family":"Messtorff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Riebeling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Nische","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Schmitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Hinrich","family":"Br\u00e4sen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Kunzendorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7768-2132","authenticated-orcid":false,"given":"Stefan","family":"Krautwald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,28]]},"reference":[{"key":"4416_CR1","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1038\/s41581-018-0052-0","volume":"14","author":"EAJ Hoste","year":"2018","unstructured":"Hoste EAJ, Kellum JA, Selby NM et al (2018) Global epidemiology and outcomes of acute kidney injury. Nat Rev Nephrol 14:607\u2013625. https:\/\/doi.org\/10.1038\/s41581-018-0052-0","journal-title":"Nat Rev Nephrol"},{"key":"4416_CR2","doi-asserted-by":"publisher","first-page":"1949","DOI":"10.1016\/S0140-6736(19)32563-2","volume":"394","author":"C Ronco","year":"2019","unstructured":"Ronco C, Bellomo R, Kellum JA (2019) Acute kidney injury. Lancet 394:1949\u20131964. https:\/\/doi.org\/10.1016\/S0140-6736(19)32563-2","journal-title":"Lancet"},{"key":"4416_CR3","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1038\/ncb3064","volume":"16","author":"JP Friedmann Angeli","year":"2014","unstructured":"Friedmann Angeli JP, Schneider M, Proneth B et al (2014) Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat Cell Biol 16:1180\u20131191. https:\/\/doi.org\/10.1038\/ncb3064","journal-title":"Nat Cell Biol"},{"key":"4416_CR4","doi-asserted-by":"publisher","first-page":"16836","DOI":"10.1073\/pnas.1415518111","volume":"111","author":"A Linkermann","year":"2014","unstructured":"Linkermann A, Skouta R, Himmerkus N et al (2014) Synchronized renal tubular cell death involves ferroptosis. Proc Natl Acad Sci USA 111:16836\u201316841. https:\/\/doi.org\/10.1073\/pnas.1415518111","journal-title":"Proc Natl Acad Sci USA"},{"key":"4416_CR5","doi-asserted-by":"publisher","first-page":"3631","DOI":"10.1007\/s00018-017-2547-4","volume":"74","author":"T M\u00fcller","year":"2017","unstructured":"M\u00fcller T, Dewitz C, Schmitz J et al (2017) Necroptosis and ferroptosis are alternative cell death pathways that operate in acute kidney failure. Cell Mol Life Sci 74:3631\u20133645. https:\/\/doi.org\/10.1007\/s00018-017-2547-4","journal-title":"Cell Mol Life Sci"},{"key":"4416_CR6","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.chembiol.2008.02.010","volume":"15","author":"WS Yang","year":"2008","unstructured":"Yang WS, Stockwell BR (2008) Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem Biol 15:234\u2013245. https:\/\/doi.org\/10.1016\/j.chembiol.2008.02.010","journal-title":"Chem Biol"},{"key":"4416_CR7","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","volume":"149","author":"SJ Dixon","year":"2012","unstructured":"Dixon SJ, Lemberg KM, Lamprecht MR et al (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149:1060\u20131072. https:\/\/doi.org\/10.1016\/j.cell.2012.03.042","journal-title":"Cell"},{"key":"4416_CR8","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.tcb.2015.10.014","volume":"26","author":"WS Yang","year":"2016","unstructured":"Yang WS, Stockwell BR (2016) Ferroptosis: death by lipid peroxidation. Trends Cell Biol 26:165\u2013176. https:\/\/doi.org\/10.1016\/j.tcb.2015.10.014","journal-title":"Trends Cell Biol"},{"key":"4416_CR9","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","volume":"171","author":"BR Stockwell","year":"2017","unstructured":"Stockwell BR, Friedmann Angeli JP, Bayir H et al (2017) Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell 171:273\u2013285. https:\/\/doi.org\/10.1016\/j.cell.2017.09.021","journal-title":"Cell"},{"key":"4416_CR10","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.cell.2013.12.010","volume":"156","author":"WS Yang","year":"2014","unstructured":"Yang WS, Sriramaratnam R, Welsch ME et al (2014) Regulation of ferroptotic cancer cell death by GPX4. Cell 156:317\u2013331. https:\/\/doi.org\/10.1016\/j.cell.2013.12.010","journal-title":"Cell"},{"key":"4416_CR11","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1038\/s41586-019-1705-2","volume":"575","author":"K Bersuker","year":"2019","unstructured":"Bersuker K, Hendricks JM, Li Z et al (2019) The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature 575:688\u2013692. https:\/\/doi.org\/10.1038\/s41586-019-1705-2","journal-title":"Nature"},{"key":"4416_CR12","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41586-019-1707-0","volume":"575","author":"S Doll","year":"2019","unstructured":"Doll S, Freitas FP, Shah R et al (2019) FSP1 is a glutathione-independent ferroptosis suppressor. Nature 575:693\u2013698. https:\/\/doi.org\/10.1038\/s41586-019-1707-0","journal-title":"Nature"},{"key":"4416_CR13","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1038\/s41586-021-03539-7","volume":"593","author":"C Mao","year":"2021","unstructured":"Mao C, Liu X, Zhang Y et al (2021) DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer. Nature 593:586\u2013590. https:\/\/doi.org\/10.1038\/s41586-021-03539-7","journal-title":"Nature"},{"key":"4416_CR14","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/s41419-021-03613-y","volume":"12","author":"H Nishizawa","year":"2021","unstructured":"Nishizawa H, Matsumoto M, Chen G et al (2021) Lipid peroxidation and the subsequent cell death transmitting from ferroptotic cells to neighboring cells. Cell Death Dis 12:332. https:\/\/doi.org\/10.1038\/s41419-021-03613-y","journal-title":"Cell Death Dis"},{"key":"4416_CR15","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1038\/s41556-020-0565-1","volume":"22","author":"M Riegman","year":"2020","unstructured":"Riegman M, Sagie L, Galed C et al (2020) Ferroptosis occurs through an osmotic mechanism and propagates independently of cell rupture. Nat Cell Biol 22:1042\u20131048. https:\/\/doi.org\/10.1038\/s41556-020-0565-1","journal-title":"Nat Cell Biol"},{"key":"4416_CR16","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1038\/s41589-021-00751-4","volume":"17","author":"M Conlon","year":"2021","unstructured":"Conlon M, Poltorack CD, Forcina GC et al (2021) A compendium of kinetic modulatory profiles identifies ferroptosis regulators. Nat Chem Biol 17:665\u2013674. https:\/\/doi.org\/10.1038\/s41589-021-00751-4","journal-title":"Nat Chem Biol"},{"key":"4416_CR17","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1021\/acscentsci.7b00028","volume":"3","author":"O Zilka","year":"2017","unstructured":"Zilka O, Shah R, Li B et al (2017) On the mechanism of cytoprotection by ferrostatin-1 and liproxstatin-1 and the role of lipid peroxidation in ferroptotic cell death. ACS Cent Sci 3:232\u2013243. https:\/\/doi.org\/10.1021\/acscentsci.7b00028","journal-title":"ACS Cent Sci"},{"issue":"Suppl 1","key":"4416_CR18","doi-asserted-by":"publisher","first-page":"S29","DOI":"10.1038\/jp.2016.30","volume":"36","author":"MJ Sankar","year":"2016","unstructured":"Sankar MJ, Chandrasekaran A, Kumar P et al (2016) Vitamin K prophylaxis for prevention of vitamin K deficiency bleeding: a systematic review. J Perinatol 36(Suppl 1):S29-35. https:\/\/doi.org\/10.1038\/jp.2016.30","journal-title":"J Perinatol"},{"key":"4416_CR19","doi-asserted-by":"publisher","first-page":"CE002776","DOI":"10.1002\/14651858.CD002776","volume":"2000","author":"RM Puckett","year":"2000","unstructured":"Puckett RM, Offringa M (2000) Prophylactic vitamin K for vitamin K deficiency bleeding in neonates. Cochrane Database Syst Rev 2000:CE002776. https:\/\/doi.org\/10.1002\/14651858.CD002776","journal-title":"Cochrane Database Syst Rev"},{"key":"4416_CR20","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.nutres.2009.03.012","volume":"29","author":"J Iwamoto","year":"2009","unstructured":"Iwamoto J, Sato Y, Takeda T et al (2009) High-dose vitamin K supplementation reduces fracture incidence in postmenopausal women: a review of the literature. Nutr Res 29:221\u2013228. https:\/\/doi.org\/10.1016\/j.nutres.2009.03.012","journal-title":"Nutr Res"},{"key":"4416_CR21","doi-asserted-by":"publisher","first-page":"2081","DOI":"10.1161\/CIRCULATIONAHA.116.027011","volume":"135","author":"VM Brandenburg","year":"2017","unstructured":"Brandenburg VM, Reinartz S, Kaesler N et al (2017) Slower progress of aortic valve calcification with vitamin K supplementation: results from a prospective interventional proof-of-concept study. Circulation 135:2081\u20132083. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.116.027011","journal-title":"Circulation"},{"key":"4416_CR22","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/j.kint.2021.10.029","volume":"101","author":"N Kaesler","year":"2022","unstructured":"Kaesler N, Schreibing F, Speer T et al (2022) Altered vitamin K biodistribution and metabolism in experimental and human chronic kidney disease. Kidney Int 101:338\u2013348. https:\/\/doi.org\/10.1016\/j.kint.2021.10.029","journal-title":"Kidney Int"},{"key":"4416_CR23","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/0003-9861(85)90365-0","volume":"241","author":"RE Talcott","year":"1985","unstructured":"Talcott RE, Smith MT, Giannini DD (1985) Inhibition of microsomal lipid peroxidation by naphthoquinones: structure-activity relationships and possible mechanisms of action. Arch Biochem Biophys 241:88\u201394. https:\/\/doi.org\/10.1016\/0003-9861(85)90365-0","journal-title":"Arch Biochem Biophys"},{"key":"4416_CR24","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1248\/cpb.39.976","volume":"39","author":"T Ohyashiki","year":"1991","unstructured":"Ohyashiki T, Yabunaka Y, Matsui K (1991) Antioxidant effect of vitamin K homologues on ascorbic acid\/Fe(2+)-induced lipid peroxidation of lecithin liposomes. Chem Pharm Bull (Tokyo) 39:976\u2013979. https:\/\/doi.org\/10.1248\/cpb.39.976","journal-title":"Chem Pharm Bull (Tokyo)"},{"key":"4416_CR25","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/0304-4165(93)90115-o","volume":"1157","author":"K Mukai","year":"1993","unstructured":"Mukai K, Morimoto H, Kikuchi S et al (1993) Kinetic study of free-radical-scavenging action of biological hydroquinones (reduced forms of ubiquinone, vitamin K and tocopherol quinone) in solution. Biochim Biophys Acta 1157:313\u2013317. https:\/\/doi.org\/10.1016\/0304-4165(93)90115-o","journal-title":"Biochim Biophys Acta"},{"key":"4416_CR26","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1016\/s0006-2952(97)00254-2","volume":"54","author":"LM Vervoort","year":"1997","unstructured":"Vervoort LM, Ronden JE, Thijssen HH (1997) The potent antioxidant activity of the vitamin K cycle in microsomal lipid peroxidation. Biochem Pharmacol 54:871\u2013876. https:\/\/doi.org\/10.1016\/s0006-2952(97)00254-2","journal-title":"Biochem Pharmacol"},{"key":"4416_CR27","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.freeradbiomed.2007.03.024","volume":"43","author":"MG Traber","year":"2007","unstructured":"Traber MG, Atkinson J (2007) Vitamin E, antioxidant and nothing more. Free Radic Biol Med 43:4\u201315. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2007.03.024","journal-title":"Free Radic Biol Med"},{"key":"4416_CR28","doi-asserted-by":"publisher","first-page":"5816","DOI":"10.1523\/JNEUROSCI.23-13-05816.2003","volume":"23","author":"J Li","year":"2003","unstructured":"Li J, Lin JC, Wang H et al (2003) Novel role of vitamin k in preventing oxidative injury to developing oligodendrocytes and neurons. J Neurosci 23:5816\u20135826","journal-title":"J Neurosci"},{"key":"4416_CR29","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.1002\/jnr.22029","volume":"87","author":"J Li","year":"2009","unstructured":"Li J, Wang H, Rosenberg PA (2009) Vitamin K prevents oxidative cell death by inhibiting activation of 12-lipoxygenase in developing oligodendrocytes. J Neurosci Res 87:1997\u20132005. https:\/\/doi.org\/10.1002\/jnr.22029","journal-title":"J Neurosci Res"},{"key":"4416_CR30","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1038\/s41418-020-00690-y","volume":"28","author":"T Riebeling","year":"2021","unstructured":"Riebeling T, Jamal K, Wilson R et al (2021) Primidone blocks RIPK1-driven cell death and inflammation. Cell Death Differ 28:1610\u20131626. https:\/\/doi.org\/10.1038\/s41418-020-00690-y","journal-title":"Cell Death Differ"},{"key":"4416_CR31","doi-asserted-by":"publisher","first-page":"F476","DOI":"10.1152\/ajprenal.00363.2006","volume":"293","author":"S Terryn","year":"2007","unstructured":"Terryn S, Jouret F, Vandenabeele F et al (2007) A primary culture of mouse proximal tubular cells, established on collagen-coated membranes. Am J Physiol-Renal Physiol 293:F476\u2013F485. https:\/\/doi.org\/10.1152\/ajprenal.00363.2006","journal-title":"Am J Physiol-Renal Physiol"},{"key":"4416_CR32","doi-asserted-by":"publisher","first-page":"F147","DOI":"10.1152\/ajprenal.00378.2013","volume":"306","author":"R Mahadevappa","year":"2014","unstructured":"Mahadevappa R, Nielsen R, Christensen EI et al (2014) Megalin in acute kidney injury: foe and friend. Am J Physiol-Renal Physiol 306:F147\u2013F154. https:\/\/doi.org\/10.1152\/ajprenal.00378.2013","journal-title":"Am J Physiol-Renal Physiol"},{"key":"4416_CR33","doi-asserted-by":"publisher","first-page":"CD000253","DOI":"10.1002\/14651858.CD000253.pub4","volume":"7","author":"JR Evans","year":"2017","unstructured":"Evans JR, Lawrenson JG (2017) Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration. Cochrane Database Syst Rev 7:CD000253. https:\/\/doi.org\/10.1002\/14651858.CD000253.pub4","journal-title":"Cochrane Database Syst Rev"},{"key":"4416_CR34","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.02523","volume":"3","author":"SJ Dixon","year":"2014","unstructured":"Dixon SJ, Patel DN, Welsch M et al (2014) Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis. Elife 3:e02523. https:\/\/doi.org\/10.7554\/eLife.02523","journal-title":"Elife"},{"key":"4416_CR35","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/nchembio.2239","volume":"13","author":"S Doll","year":"2017","unstructured":"Doll S, Proneth B, Tyurina YY et al (2017) ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat Chem Biol 13:91\u201398. https:\/\/doi.org\/10.1038\/nchembio.2239","journal-title":"Nat Chem Biol"},{"key":"4416_CR36","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1016\/j.bbrc.2016.08.124","volume":"478","author":"H Yuan","year":"2016","unstructured":"Yuan H, Li X, Zhang X et al (2016) Identification of ACSL4 as a biomarker and contributor of ferroptosis. Biochem Biophys Res Commun 478:1338\u20131343. https:\/\/doi.org\/10.1016\/j.bbrc.2016.08.124","journal-title":"Biochem Biophys Res Commun"},{"key":"4416_CR37","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1021\/acschembio.5b00245","volume":"10","author":"SJ Dixon","year":"2015","unstructured":"Dixon SJ, Winter GE, Musavi LS et al (2015) Human haploid cell genetics reveals roles for lipid metabolism genes in nonapoptotic cell death. ACS Chem Biol 10:1604\u20131609. https:\/\/doi.org\/10.1021\/acschembio.5b00245","journal-title":"ACS Chem Biol"},{"key":"4416_CR38","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101328","volume":"28","author":"G Miotto","year":"2020","unstructured":"Miotto G, Rossetto M, Di Paolo ML et al (2020) Insight into the mechanism of ferroptosis inhibition by ferrostatin-1. Redox Biol 28:101328. https:\/\/doi.org\/10.1016\/j.redox.2019.101328","journal-title":"Redox Biol"},{"key":"4416_CR39","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/s0891-5849(02)00848-1","volume":"33","author":"GP Drummen","year":"2002","unstructured":"Drummen GP, van Liebergen LC, Op den Kamp JA et al (2002) C11-BODIPY(581\/591), an oxidation-sensitive fluorescent lipid peroxidation probe: (micro)spectroscopic characterization and validation of methodology. Free Radic Biol Med 33:473\u2013490. https:\/\/doi.org\/10.1016\/s0891-5849(02)00848-1","journal-title":"Free Radic Biol Med"},{"key":"4416_CR40","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1016\/s0891-5849(01)00684-0","volume":"31","author":"G Aldini","year":"2001","unstructured":"Aldini G, Yeum KJ, Russell RM et al (2001) A method to measure the oxidizability of both the aqueous and lipid compartments of plasma. Free Radic Biol Med 31:1043\u20131050. https:\/\/doi.org\/10.1016\/s0891-5849(01)00684-0","journal-title":"Free Radic Biol Med"},{"key":"4416_CR41","doi-asserted-by":"publisher","first-page":"1798","DOI":"10.1182\/blood.V93.6.1798.406k22_1798_1808","volume":"93","author":"B Furie","year":"1999","unstructured":"Furie B, Bouchard BA, Furie BC (1999) Vitamin K-dependent biosynthesis of gamma-carboxyglutamic acid. Blood 93:1798\u20131808","journal-title":"Blood"},{"key":"4416_CR42","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1089\/ars.2006.8.347","volume":"8","author":"J Oldenburg","year":"2006","unstructured":"Oldenburg J, Bevans CG, M\u00fcller CR et al (2006) Vitamin K epoxide reductase complex subunit 1 (VKORC1): the key protein of the vitamin K cycle. Antioxid Redox Signal 8:347\u2013353. https:\/\/doi.org\/10.1089\/ars.2006.8.347","journal-title":"Antioxid Redox Signal"},{"key":"4416_CR43","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1055\/s-2007-996417","volume":"25","author":"KO Haustein","year":"1999","unstructured":"Haustein KO (1999) Pharmacokinetic and pharmacodynamic properties of oral anticoagulants, especially phenprocoumon. Semin Thromb Hemost 25:5\u201311. https:\/\/doi.org\/10.1055\/s-2007-996417","journal-title":"Semin Thromb Hemost"},{"key":"4416_CR44","doi-asserted-by":"publisher","unstructured":"Moerke C, Teilig F, Kunzendorf U et al (2019) ACSL4 as the first reliable biomarker of ferroptosis under pathophysiological conditions. In: Tang D (ed) Ferroptosis in health and disease. Springer, Berlin, pp 111\u2013123. https:\/\/doi.org\/10.1007\/978-3-030-26780-3_7","DOI":"10.1007\/978-3-030-26780-3_7"},{"key":"4416_CR45","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/j.tips.2017.02.005","volume":"38","author":"JPF Angeli","year":"2017","unstructured":"Angeli JPF, Shah R, Pratt DA et al (2017) Ferroptosis inhibition: mechanisms and opportunities. Trends Pharmacol Sci 38:489\u2013498. https:\/\/doi.org\/10.1016\/j.tips.2017.02.005","journal-title":"Trends Pharmacol Sci"},{"key":"4416_CR46","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1016\/s0005-2736(99)00239-4","volume":"1463","author":"A Bridge","year":"2000","unstructured":"Bridge A, Barr R, Morre DJ (2000) The plasma membrane NADH oxidase of soybean has vitamin K(1) hydroquinone oxidase activity. Biochim Biophys Acta 1463:448\u2013458. https:\/\/doi.org\/10.1016\/s0005-2736(99)00239-4","journal-title":"Biochim Biophys Acta"},{"key":"4416_CR47","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1126\/science.1218632","volume":"336","author":"M Vos","year":"2012","unstructured":"Vos M, Esposito G, Edirisinghe JN et al (2012) Vitamin K2 is a mitochondrial electron carrier that rescues pink1 deficiency. Science 336:1306\u20131310. https:\/\/doi.org\/10.1126\/science.1218632","journal-title":"Science"},{"key":"4416_CR48","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/nchembio.2238","volume":"13","author":"VE Kagan","year":"2017","unstructured":"Kagan VE, Mao G, Qu F et al (2017) Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat Chem Biol 13:81\u201390. https:\/\/doi.org\/10.1038\/nchembio.2238","journal-title":"Nat Chem Biol"},{"key":"4416_CR49","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/s41556-021-00818-3","volume":"24","author":"HL Zhang","year":"2022","unstructured":"Zhang HL, Hu BX, Li ZL et al (2022) PKCbetaII phosphorylates ACSL4 to amplify lipid peroxidation to induce ferroptosis. Nat Cell Biol 24:88\u201398. https:\/\/doi.org\/10.1038\/s41556-021-00818-3","journal-title":"Nat Cell Biol"},{"key":"4416_CR50","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01641","author":"S Hofmans","year":"2016","unstructured":"Hofmans S, Berghe TV, Devisscher L et al (2016) Novel ferroptosis inhibitors with improved potency and ADME properties. J Med Chem. https:\/\/doi.org\/10.1021\/acs.jmedchem.5b01641","journal-title":"J Med Chem"},{"key":"4416_CR51","first-page":"239","volume":"10","author":"N Mobarra","year":"2016","unstructured":"Mobarra N, Shanaki M, Ehteram H et al (2016) A review on iron chelators in treatment of iron overload syndromes. Int J Hematol Oncol Stem Cell Res 10:239\u2013247","journal-title":"Int J Hematol Oncol Stem Cell Res"},{"key":"4416_CR52","doi-asserted-by":"publisher","first-page":"37","DOI":"10.7326\/0003-4819-142-1-200501040-00110","volume":"142","author":"ER Miller 3rd","year":"2005","unstructured":"Miller ER 3rd, Pastor-Barriuso R, Dalal D et al (2005) Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 142:37\u201346. https:\/\/doi.org\/10.7326\/0003-4819-142-1-200501040-00110","journal-title":"Ann Intern Med"},{"key":"4416_CR53","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1016\/j.kint.2021.06.037","volume":"100","author":"N Kaesler","year":"2021","unstructured":"Kaesler N, Schurgers LJ, Floege J (2021) Vitamin K and cardiovascular complications in chronic kidney disease patients. Kidney Int 100:1023\u20131036. https:\/\/doi.org\/10.1016\/j.kint.2021.06.037","journal-title":"Kidney Int"},{"key":"4416_CR54","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1001\/archsurg.1962.01300220073012","volume":"84","author":"D Agostino","year":"1962","unstructured":"Agostino D, Cliffton EE (1962) Anticoagulants and the development of pulmonary metastases. Anticoagulant effect on the Walker 256 carcinosarcoma in rats. Arch Surg 84:449\u2013453. https:\/\/doi.org\/10.1001\/archsurg.1962.01300220073012","journal-title":"Arch Surg"},{"key":"4416_CR55","first-page":"1217","volume":"33","author":"JM Brown","year":"1973","unstructured":"Brown JM (1973) A study of the mechanism by which anticoagulation with warfarin inhibits blood-borne metastases. Cancer Res 33:1217\u20131224","journal-title":"Cancer Res"},{"key":"4416_CR56","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/0014-2964(79)90058-6","volume":"15","author":"P Hilgard","year":"1979","unstructured":"Hilgard P, Maat B (1979) Mechanism of lung tumour colony reduction caused by coumarin anticoagulation. Eur J Cancer 15:183\u2013187. https:\/\/doi.org\/10.1016\/0014-2964(79)90058-6","journal-title":"Eur J Cancer"},{"key":"4416_CR57","doi-asserted-by":"publisher","first-page":"5103","DOI":"10.1038\/s41467-021-25354-4","volume":"12","author":"W Liu","year":"2021","unstructured":"Liu W, Chakraborty B, Safi R et al (2021) Dysregulated cholesterol homeostasis results in resistance to ferroptosis increasing tumorigenicity and metastasis in cancer. Nat Commun 12:5103. https:\/\/doi.org\/10.1038\/s41467-021-25354-4","journal-title":"Nat Commun"},{"key":"4416_CR58","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1038\/s41586-020-2623-z","volume":"585","author":"JM Ubellacker","year":"2020","unstructured":"Ubellacker JM, Tasdogan A, Ramesh V et al (2020) Lymph protects metastasizing melanoma cells from ferroptosis. Nature 585:113\u2013118. https:\/\/doi.org\/10.1038\/s41586-020-2623-z","journal-title":"Nature"},{"key":"4416_CR59","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1097\/COC.0000000000000571","volume":"42","author":"M Shurrab","year":"2019","unstructured":"Shurrab M, Quinn KL, Kitchlu A et al (2019) Long-term vitamin K antagonists and cancer risk: a systematic review and meta-analysis. Am J Clin Oncol 42:717\u2013724. https:\/\/doi.org\/10.1097\/COC.0000000000000571","journal-title":"Am J Clin Oncol"},{"key":"4416_CR60","doi-asserted-by":"publisher","first-page":"2046","DOI":"10.1002\/1097-0142(19840515)53:10<2046::aid-cncr2820531007>3.0.co;2-f","volume":"53","author":"LR Zacharski","year":"1984","unstructured":"Zacharski LR, Henderson WG, Rickles FR et al (1984) Effect of warfarin anticoagulation on survival in carcinoma of the lung, colon, head and neck, and prostate. Final report of VA Cooperative Study #75. Cancer 53:2046\u20132052. https:\/\/doi.org\/10.1002\/1097-0142(19840515)53:10%3c2046::aid-cncr2820531007%3e3.0.co;2-f","journal-title":"Cancer"},{"key":"4416_CR61","doi-asserted-by":"publisher","first-page":"2048","DOI":"10.1038\/s41467-021-22336-4","volume":"12","author":"CM Bebber","year":"2021","unstructured":"Bebber CM, Thomas ES, Stroh J et al (2021) Ferroptosis response segregates small cell lung cancer (SCLC) neuroendocrine subtypes. Nat Commun 12:2048. https:\/\/doi.org\/10.1038\/s41467-021-22336-4","journal-title":"Nat Commun"},{"key":"4416_CR62","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41586-019-1170-y","volume":"569","author":"W Wang","year":"2019","unstructured":"Wang W, Green M, Choi JE et al (2019) CD8(+) T cells regulate tumour ferroptosis during cancer immunotherapy. Nature 569:270\u2013274. https:\/\/doi.org\/10.1038\/s41586-019-1170-y","journal-title":"Nature"},{"key":"4416_CR63","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz745.1125","author":"H Bonnemeier","year":"2019","unstructured":"Bonnemeier H, Kreutz R, Enders D et al (2019) P4749Renal function worsening in factor-xa inhibitors vs phenprocoumon in patients with non-valvular atrial fibrillation and renal disease\u2014insights from the RELOADED study. Eur Heart J. https:\/\/doi.org\/10.1093\/eurheartj\/ehz745.1125","journal-title":"Eur Heart J"},{"key":"4416_CR64","doi-asserted-by":"publisher","first-page":"2272","DOI":"10.1016\/j.jacc.2016.08.063","volume":"68","author":"YH Chan","year":"2016","unstructured":"Chan YH, Yeh YH, See LC et al (2016) Acute kidney injury in asians with atrial fibrillation treated with Dabigatran or Warfarin. J Am Coll Cardiol 68:2272\u20132283. https:\/\/doi.org\/10.1016\/j.jacc.2016.08.063","journal-title":"J Am Coll Cardiol"},{"key":"4416_CR65","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.thromres.2018.12.010","volume":"174","author":"C Zhang","year":"2019","unstructured":"Zhang C, Gu ZC, Ding Z et al (2019) Decreased risk of renal impairment in atrial fibrillation patients receiving non-vitamin K antagonist oral anticoagulants: a pooled analysis of randomized controlled trials and real-world studies. Thromb Res 174:16\u201323. https:\/\/doi.org\/10.1016\/j.thromres.2018.12.010","journal-title":"Thromb Res"},{"key":"4416_CR66","doi-asserted-by":"publisher","first-page":"2787","DOI":"10.1681\/ASN.2018070741","volume":"29","author":"S Brodsky","year":"2018","unstructured":"Brodsky S, Eikelboom J, Hebert LA (2018) Anticoagulant-related nephropathy. J Am Soc Nephrol 29:2787\u20132793. https:\/\/doi.org\/10.1681\/ASN.2018070741","journal-title":"J Am Soc Nephrol"},{"key":"4416_CR67","doi-asserted-by":"publisher","first-page":"935","DOI":"10.2215\/CJN.02470319","volume":"14","author":"RJ Glassock","year":"2019","unstructured":"Glassock RJ (2019) Anticoagulant-related nephropathy: it\u2019s the real McCoy. Clin J Am Soc Nephrol 14:935\u2013937. https:\/\/doi.org\/10.2215\/CJN.02470319","journal-title":"Clin J Am Soc Nephrol"},{"key":"4416_CR68","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.617786","author":"AK Medipally","year":"2021","unstructured":"Medipally AK, Xiao M, Qaisar S et al (2021) Anticoagulant related nephropathy only partially develops in C57BL\/6 mice: hematuria is not accompanied by red blood cell casts in the kidney. Front Med. https:\/\/doi.org\/10.3389\/fmed.2020.617786","journal-title":"Front Med"},{"key":"4416_CR69","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/ki.2011.44","volume":"80","author":"SV Brodsky","year":"2011","unstructured":"Brodsky SV, Nadasdy T, Rovin BH et al (2011) Warfarin-related nephropathy occurs in patients with and without chronic kidney disease and is associated with an increased mortality rate. Kidney Int 80:181\u2013189. https:\/\/doi.org\/10.1038\/ki.2011.44","journal-title":"Kidney Int"},{"key":"4416_CR70","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1053\/j.ajkd.2009.04.024","volume":"54","author":"SV Brodsky","year":"2009","unstructured":"Brodsky SV, Satoskar A, Chen J et al (2009) Acute kidney injury during warfarin therapy associated with obstructive tubular red blood cell casts: a report of 9 cases. Am J Kidney Dis 54:1121\u20131126. https:\/\/doi.org\/10.1053\/j.ajkd.2009.04.024","journal-title":"Am J Kidney Dis"},{"key":"4416_CR71","doi-asserted-by":"publisher","first-page":"1856","DOI":"10.1681\/ASN.2010101110","volume":"22","author":"K Ware","year":"2011","unstructured":"Ware K, Brodsky P, Satoskar AA et al (2011) Warfarin-related nephropathy modeled by nephron reduction and excessive anticoagulation. J Am Soc Nephrol 22:1856\u20131862. https:\/\/doi.org\/10.1681\/ASN.2010101110","journal-title":"J Am Soc Nephrol"},{"key":"4416_CR72","doi-asserted-by":"publisher","first-page":"F1421","DOI":"10.1152\/ajprenal.00689.2012","volume":"304","author":"K Ware","year":"2013","unstructured":"Ware K, Qamri Z, Ozcan A et al (2013) N-acetylcysteine ameliorates acute kidney injury but not glomerular hemorrhage in an animal model of warfarin-related nephropathy. Am J Physiol Renal Physiol 304:F1421-1427. https:\/\/doi.org\/10.1152\/ajprenal.00689.2012","journal-title":"Am J Physiol Renal Physiol"}],"container-title":["Cellular and Molecular Life Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00018-022-04416-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00018-022-04416-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00018-022-04416-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T05:31:51Z","timestamp":1659591111000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00018-022-04416-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,28]]},"references-count":72,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["4416"],"URL":"https:\/\/doi.org\/10.1007\/s00018-022-04416-w","relation":{},"ISSN":["1420-682X","1420-9071"],"issn-type":[{"value":"1420-682X","type":"print"},{"value":"1420-9071","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,28]]},"assertion":[{"value":"4 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 May 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 June 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 June 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All experiments were carried out in accordance with the guidelines for Animal Care of the Christian-Albrechts-University of Kiel.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}],"article-number":"387"}}