Multi-Tasking:NuclearTranscriptionFactorswithNovelRolesintheMitochondriaKarolSzczepanek1,2,EdwardJ.Lesnefsky1,2,3,andAndrewC.Larner1,41DepartmentofBiochemistryandMolecularBiology,andMasseyCancerCenter,VirginiaCommonwealthUniversity,Richmond,VA23298,USA2DepartmentofInternalMedicine,DivisionofCardiology-PauleyHeartCenter,VirginiaCommonwealthUniversity,Richmond,VA23298,USA3MedicalService,McGuireDepartmentofVeteransAffairsMedicalCenter,Richmond,VA23249,USAAbstractCoordinatedresponsesbetweenthenucleusandmitochondriaareessentialformaintenanceofhomeostasis.Forover15years,poolsofnucleartranscriptionfactors(TFs),suchasp53andnuclearhormonereceptors,havebeenobservedinthemitochondria.ThecontributionofthemitochondrialpooloftheseTFstotheirwell-definedbiologicalactionsisinsomecasesclearandinothersnotwellunderstood.Recently,asmallmitochondrialpooloftheTFsignaltransducerandactivatoroftranscriptionfactor3(STAT3)wasshowntomodulatetheactivityoftheelectrontransportchain.ThemitochondrialfunctionofSTAT3encompassesbothitsbiologicalactionsintheheartaswellasitsoncogeniceffects.ThisreviewhighlightsadvancesinourunderstandingofhowmitochondrialpoolsofnuclearTFsmayinfluencethefunctionofthisorganelle.Keywordsnucleartranscriptionfactors;mitochondrialfunction;apoptosis;STAT3NuclearTranscriptionFactorsintheMitochondriaSeveralreportshaveshownthatpoolsofnucleartranscriptionfactorswithwell-characterizedfunctionsinthenucleusarealsopresentinthemitochondria(mitoTFs)[1–11].MitoTFscomprisethoseofthenuclearhormonereceptorfamilyaswellastranscriptionfactors(e.g.p53,NF-κBandtheSTATs)thatareactivateddownstreamofgrowthhormonesandcytokinesbindingtocellsurfacereceptors.Themitochondrialfunctionofnuclearhormonereceptorshasbeenrecentlyreviewed[4,6]andwillnotbediscussedhere.Rather,wewillsummarizeourunderstandingoftheactionsofmitoTFswhoseactivitiesaremediatedbyhormonesandcytokinesthatbindcellsurfacereceptors.Ingeneral,thefractionofTFsinthemitochondriaisverysmallcomparedtothelevelsinthecytosolornucleus(5–10%).Thepot...
