ContentslistsavailableatScienceDirectSeminarsinCancerBiologyjournalhomepage:www.elsevier.com/locate/semcancerReviewMitochondrialbiologyincancerstemcellsRuteLoureiroa,1,KatiaA.Mesquitab,1,SilviaMagalhães-Novaisb,PauloJ.Oliveirab,IgnacioVega-Naredob,c,⁎aMax-PlanckInstituteforMetabolismResearch,50931Cologne,GermanybCNC-CenterforNeuroscienceandCellBiology,UniversityofCoimbra,UCBiotechBuilding,BiocantPark,3060-197Cantanhede,PortugalcDepartmentofMorphologyandCellBiology,UniversityofOviedo,33006Oviedo,SpainARTICLEINFOKeywords:MitochondriaCancerstemcellsMetabolismChemotherapyCelldeathABSTRACTCancerstemcells(CSCs)havebeensuggestedtoberesponsiblefortumorre-growthandrelapse.PhysiologicalandmorphologicalknowledgeofCSCsmaybeessentialforthedevelopmentofnewtherapeuticstrategiestargetingcancerdevelopment,progression,andrecurrence.Currentresearchisfocusedonadeeperunder-standingofCSCsmetabolicprofiles,takingintoconsiderationtheirenergydemands.Energymetabolismandmitochondrialfunctionareimportantfactorsoperatingonstemnessmaintenanceandcellfatespecification.Duetotheroleofmitochondriaascentralhubsintheoverallcellmetabolismanddeathandsurvivalpathways,researchontheirphysiologyinCSCsisofparamountimportancetodeciphermechanismsunderlyingtheirtherapy-resistantphenotype.Inthisreview,wefocusonCSCsmitochondrialbiologyandmitochondria-relatedsignalingpathwaysthatcontributetoCSCssurvivalandmaintenance,therebyrepresentingpossibletherapeutictargets.1.IntroductionTheexistenceofdifferenttumortypesandtheconceptoftumorheterogeneitywereproposeddecadesago,beingnowwidelyaccepted[1].Suchheterogeneityisrepresentedbydifferentialtumorcellpo-pulationswithdistinctproliferativeanddifferentiationcapacitieswithinthesametumorbulk.PioneeringstudiesfromHewittetal.[2]togetherwithalaterworkfromLapidotetal.[3]supportedtheideaoftumorheterogeneity,andsuggestedthehypothesisofcancerstemcells(CSCs)astumor-initiatingcells.FurtherstudiesbyJohnDickandcol-leagues[4]replicatedandtransferredthesefindingstodifferenttumortypessuch...
