AutophagyandTumorMetabolismAlecC.Kimmelman1andEileenWhite2,31PerlmutterCancerCenter,DepartmentofRadiationOncology,NYUMedicalSchool,NewYork,NY100162RutgersCancerInstituteofNewJersey,NewBrunswick,NJ089033DepartmentofMolecularBiologyandBiochemistry,RutgersUniversity,Piscataway,NJ,08854AbstractAutophagyisacriticalcellularprocessthatgenerallyprotectscellsandorganismsfromstressorssuchasnutrientdeprivation.Inadditiontoitsroleinnormalphysiology,autophagyplaysaroleinpathologicalprocessessuchascancer.Indeed,therehasbeensubstantialworkexploringthecomplexandcontext-dependentroleofautophagyincancer.Oneoftheemergingthemesisthatincertaincancertypes,autophagyisimportanttosupporttumorgrowthandthereforeinhibitingautophagyasatherapeuticapproachisactivelybeingtestedinclinicaltrials.Akeymechanismofhowautophagypromotesthegrowthandsurvivalofvariouscancersisitsabilitytosupportcellularmetabolism.Thediversemetabolicfuelsourcesthatcanbeproducedbyautophagyprovidestumorswithmetabolicplasticityandcanallowthemtothriveinwhatcanbeanausteremicroenvironment.Therefore,understandinghowautophagycanfuelcellularmetabolismwillenablemoreeffectivecombinatorialtherapeuticstrategies.IntroductionMacroautophagy(hereafterreferredtoasautophagy)isacatabolicprocesswherebyintracellularcomponents(cargo)areenvelopedindouble-membranedvesicles,knownasanautophagososomes,whichultimatelyfusewithlysosomeswherethecontentsaredegradedandrecycledintothecytosol(LevineandKlionsky,2004).Inadditiontomacroautophagy,therearetwoadditionaltypesofautophagy,microautophagyandchaperone-mediatedautophagy,whichdifferinhowtheparticularcargoisdeliveredtolysosomesandarethesubjectofseveralexcellentreviews(BejaranoandCuervo,2010;KonandCuervo,2010;Mijaljicaetal.,2011).CorrespondingAuthors:Dr.AlecKimmelman,PerlmutterCancerCenter,DepartmentofRadiationOncology,NYUMedicalSchool,NewYork,NY10016.V:646.501.8940.Alec.Kimmelman@nyumc.org,(leadcontact);Dr.EileenWhite,RutgersCancerInstituteofNewJersey,195LittleAlbanyStreet,NewBrunswick,NJ08903-2681,V:732-2...
