LeadingEdgePreviewsTransformingLipoxygenases:PE-SpecificEnzymesinDisguiseLingF.Ye1andBrentR.Stockwell1,2,*1DepartmentofBiologicalSciences2DepartmentofChemistryColumbiaUniversity,550West120thStreet,MC4846,NewYork,NY10027,USA*Correspondence:bstockwell@columbia.eduhttps://doi.org/10.1016/j.cell.2017.10.006InthisissueofCell,Wenzeletal.solvealong-standingmysteryregardinghowdamagetocellmem-branesoccursduringferroptosis,aniron-dependentformofregulatedcelldeath.TheyfoundthatlipoxygenasesarelikeTransformertoys,beingconvertedfromoneenzymetypetoanotherinthepresenceoftheproteinPEBP1.Cellsareboundedbygreasylipidmole-culesthatactasabarriertowater,sepa-ratingdifferentcompartmentsofthecell,aswellasseparatingtheoutsideworldfromtheinsideofthecell(AgmonandStockwell,2017).Themostcommonclassofmembranelipidsisbuiltfromacombinationoftwokindsofmolecules:apolarheadgroupthatcontainstheelementphosphorusandoneormorefattyacidtailsthatcontainalongstringofcarbonatoms.Onceconstructed,theselipidsarereferredtoasphospho-lipids.Thefattyacidpartofthephospho-lipidcanbesaturated(meaningthattherearenocarbon-carbondoublebonds),monounsaturated(meaningthatthereisonecarbon-carbondoublebond),orpoly-unsaturated(meaningthatthereismorethanonecarbon-carbondoublebond);onlythelatterspeciesissensitivetore-actingwithoxygeninachemicalreactionreferredtoasperoxidation(GaschlerandStockwell,2017).Ithasbeenpreviouslyestablishedthatcelldeathbyferroptosisisaresultofsuchlipidperoxidation(Yangetal.,2016;YangandStockwell,2016).Inthischemicalreaction,oxygenisaddedtopolyunsaturatedtailsofphospholipidsincellmembranes,creatingnewtypesofmoleculesknownaslipidhydroperox-ides,aswellasotherderivativespeciesthatmayinterferewiththeassemblyandstructureofcellularlipidmembranes.Insomecases,thisprocesscanbecata-lyzedbyaclassofenzymesknownaslipoxygenases.Whilethephysiologicalfunctionsoflipoxygenasesarenumerous,theyareperhapsbestknownfortheirroleingeneratingleukotrienes,whicharecar-bon-richlipidsignalingmoleculesthatplayimportantrolesininflam...
