Respiratory Chain Complexes in Dynamic Mitochondria Display a Patchy Distribution in Life Cells 英文参考文献.docVIP

RespiratoryChainComplexesinDynamicMitochondria DisplayaPatchyDistributioninLifeCells BrittaMuster1,WladislawKohl1,2,IlkaWittig3,ValentinaStrecker3,FriederikeJoos4,WinfriedHaase4, Ju¨rgenBereiter-Hahn1,KarinBusch1,2* 1InstituteofKinematicCellResearch,DepartmentofBiology,UniversityofFrankfurt,Frankfurt/Main,Germany,2LaboratoryforMitochondrialDynamics,Departmentof Biology, University of Osnabrueck, Osnabrueck, Germany, 3Institute of Molecular Bioenergetics, Medical School, University of Frankfurt, Frankfurt/Main, Germany, 4ElectronFacility,MaxPlanckInstituteofBiophysics,Frankfurt/Main,Germany Abstract Background:Mitochondria,themainsuppliersofcellularenergy,aredynamicorganellesthatfuseanddividefrequently. Constrainingtheseprocessesimpairsmitochondrialiscloselylinkedtocertainneurodegenerativediseases.Itisproposed thatfunctionalmitochondrialdynamicsallowstheexchangeofcompoundstherebyprovidingarescuemechanism. Methodology/Principal Findings: The question discussed in this paper is whether fusion and fission of mitochondria in differentcelllinesresultinre-localizationofrespiratorychain(RC)complexesandoftheATPsynthase.Thiswasaddressed by fusing cells containing mitochondria with respiratory complexes labelled with different fluorescent proteins and resolvingtheirtimedependentre-localizationinlivingcells.WefoundacompletereshufflingofRCcomplexesthroughout the entire chondriome in single HeLa cells within 2–3h by organelle fusion and fission. Polykaryons of fused cells completely re-mixed their RC complexes in 10–24h in a progressive way. In contrast to the recently described homogeneousmixingofmatrix-targetedproteinsoroutermembraneproteins,thedistributionofRCcomplexesandATP synthase in fused hybrid mitochondria, however, was not homogeneous but patterned. Thus, complete equilibration of respiratorychaincomplexesasintegralinnermitochondrialmembranecomplexesisaslowprocesscomparedwithmatrix proteins probably limited by complete fusion. In co-expressing cells, complex II is mo