Toeatornottoeat—themetabolicflavorofferroptosisMinghuiGao1,2andXuejunJiang2Ferroptosisisanewlydefinediron-dependent,non-apoptoticmodeofcelldeathwithnecroticmorphology.Distinctivefromotherdeathmechanisms,ferroptosisrequirescellularironandlipidperoxides,andisdictatedbyspecificcellularmetabolicprocesses.Importantly,ferroptosishasbeenimplicatedinaplethoraofhumandiseases.Thispaperreviewstherecentadvancesandoutstandingquestionsofthefieldbyfocusingontheroleofcellularmetabolisminferroptosis.Therelevanceofferroptosistodiseaseandtherapyisalsodiscussed.Addresses1HITCenterforLifeSciences,SchoolofLifeScienceandTechnology,HarbinInstituteofTechnology,Harbin150080,China2CellBiologyProgram,MemorialSloan-KetteringCancerCenter,1275YorkAvenue,NewYork,NY10065,USACorrespondingauthors:Gao,Minghui(gaominghui@hotmail.com),Jiang,Xuejun(jiangx@mskcc.org)CurrentOpinioninCellBiology2018,51:58–64ThisreviewcomesfromathemedissueonCellsignallingEditedbyBarryThompsonandFilippoGiancottihttps://doi.org/10.1016/j.ceb.2017.11.0010955-0674/ã2017ElsevierLtd.Allrightsreserved.IntroductionDeathisthecommonfateofalllivingmatters,includingeverycellinourbodies.Althoughoftendetrimentalandasignofdeterioration,celldeathcanalsobeanintegralpartoflifeandbeharnessed,orprogrammed,tobenefitthemulticellularorganism,thustheconceptof‘programmedcelldeath’(PCD).Forexample,spatiallyandtemporallyorchestratedPCDiscriticalinshapingthestructureandfunctionofdevelopingtissuesandorgans,andprecisePCDofimmunecellsenablesproperimmuneresponsewithoutyieldingautoimmunedisorders.Conversely,mal-functionofPCDcontributestothedevelopmentofvariousdiseases,suchascancer,immunediseases,andneurodegeneration[1–5].TwocriterianeedtobesatisfiedforthestrictqualificationofPCD:(1)thedeathprocessisgeneticallyprogrammed,thatis,thefunctionofcertaingeneproduct(s)isrequiredfortheexecution(NOTonlyinhibition)ofcelldeath;and(2)thedeathprocessbenefitstheorganismunderspecificbiologicalcontexts.However,inthisreviewandnumer-ousotherpublicationsinthePCDfield,...
