Ferroptosis:deathbylipidperoxidationWanSeokYang1,*,4andBrentR.Stockwell1,2,3,*1DepartmentofBiologicalSciences,HowardHughesMedicalInstitute,ColumbiaUniversity,NewYork,NY,USA2DepartmentofChemistry,ColumbiaUniversity,NewYork,NY,USA3DepartmentofSystemsBiology,ColumbiaUniversity,NewYork,NY,USAAbstractFerroptosisisaregulatedformofcelldeathdrivenbylossofactivityofthelipidrepairenzymeglutathioneperoxidase4(GPX4)andsubsequentaccumulationoflipid-basedreactiveoxygenspecies,particularlylipidhydroperoxides.Thisformofiron-dependentcelldeathisgenetically,biochemically,andmorphologicallydistinctfromothercelldeathmodalities,includingapoptosis,unregulatednecrosis,andnecroptosis.Ferroptosisisregulatedbyspecificpathwaysandisinvolvedindiversebiologicalcontexts.Here,wesummarizethediscoveryofferroptosis,themechanismofferroptosisregulation,anditsincreasinglyappreciatedrelevancetobothnormalandpathologicalphysiology.Keywordsferroptosis;GPX4;systemxc−;lipidperoxides;ROS;celldeathDiscoveryofferroptosisCelldeathisessentialforfundamentalphysiologicalprocesses,suchasdevelopment,immunity,andtissuehomeostasis;moreover,celldeathisoftendysregulatedindegenerativeandneoplasticdiseases.Bothapoptoticandnon-apoptoticcelldeathmodalitieshaveincreasinglybeennecessarytoexplaindiversebiologicalprocessesinvolvingcellloss.Tworegulatedformsofnon-apoptoticcelldeath,necroptosisandferroptosis,havebeenshownrecentlytoplaysignificantrolesinnumerousbiologicalcontexts[1,2].Whilethemechanismsandphysiologicalrelevanceofnecroptosishavebeenreviewedrecently[3],wefocushereonthemolecularmechanismscontrollingferroptosisanditsrelevancetohealthanddisease.Correspondingauthors:Yang,W.S.(yangw@stjohns.edu);Stockwell,B.R.(bstockwell@columbia.edu).4Presentaddress:DepartmentofBiologicalSciences,St.John’sUniversity,Queens,NY,USAPublisher'sDisclaimer:ThisisaPDFfileofanuneditedmanuscriptthathasbeenacceptedforpublication.Asaservicetoourcustomersweareprovidingthisearlyversionofthemanuscript.Themanuscriptwillundergocopyediting,typesettin...
