CellResearch(2018)28:9-21.www.nature.com/crREVIEWPlasmamembranechangesduringprogrammedcelldeathsYingyingZhang1,XinChen1,CyrilGueydan2,JiahuaiHan11StateKeyLaboratoryofCellularStressBiology,InnovationCenterforCellSignalingNetwork,SchoolofLifeSciences,XiamenUniversity,Xiamen,Fujian361005,China;2LaboratoiredeBiologieMoléculaireduGène,FacultédesSciences,UniversitéLibredeBruxelles,1050Brussels,BelgiumRupturedandintactplasmamembranesareclassicallyconsideredashallmarksofnecroticandapoptoticcelldeath,respectively.Assuch,apoptosisisusuallyconsideredanon-inflammatoryprocesswhilenecrosistriggersin-flammation.Recentstudiesonnecroptosisandpyroptosis,twotypesofprogrammednecrosis,revealedthatplasmamembraneruptureismediatedbyMLKLchannelsduringnecroptosisbutdependsonnon-selectivegasderminD(GSDMD)poresduringpyroptosis.Importantly,themorphologyofdyingcellsexecutedbyMLKLchannelscanbedistinguishedfromthatexecutedbyGSDMDpores.Interestingly,itwasfoundrecentlythatsecondarynecrosisofapoptoticcells,apreviouslybelievednon-regulatedformofcelllysisthatoccursafterapoptosis,canbeprogrammedandexecutedbyplasmamembraneporeformationlikethatofpyroptosis.Inaddition,pyroptosisisassociatedwithpyroptoticbodies,whichhavesomesimilaritiestoapoptoticbodies.Therefore,differentcelldeathprogramsinducedistinctivereshufflingprocessesoftheplasmamembrane.Giventhefactthatthenatureofreleasedintracellularcontentsplaysacrucialroleindying/deadcell-inducedimmunogenicity,notonlymembraneruptureorintegritybutalsothenatureofplasmamembranebreakdownwoulddeterminethefateofacellaswellasitsabilitytoelicitanimmuneresponse.Inthisreview,wewilldiscussrecentadvancesinthefieldofapoptosis,necroptosisandpyroptosis,withanemphasisonthemechanismsunderlyingplasmamembranechangesobservedondyingcellsandtheirimpli-cationincelldeath-elicitedimmunogenicity.Keywords:programmedcelldeath;plasmamembrane;mechanism;morphology;immunologyCellResearch(2018)28:9-21.doi:10.1038/cr.2017.133;publishedonline27October2017Correspondence:JiahuaiHanE-mail:jhan...