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Thursday9/82016
MikeMueckler
[email protected]
IntracellularTarge?ngofNascentPolypep?des
MitochondriaaretheSitesof
Oxida?veATPProduc?on
Sugars
Figure 14-10 Molecular Biology of the Cell (© Garland Science 2008)
Triglycerides
MitochondrialBiogenesis
•  Mitochondriacontaintheirowngenomeand
proteinsynthe3cmachinery(tRNAs,mRNAs,
ribosomes,ini3a3onandelonga3onfactors,etc.)
•  Mitochondriaarecomprisedofhundredsof
dis3nctproteins,onlyahandfulofwhichare
encodedinthemitochondrialgenome(variesby
species)
•  Mostmitochondrialproteinsareencodedin
nuclearDNA,synthesizedinthecytosol,and
importedpost-transla3onallyintotheorganelle
MitochondriaPossess4Subcompartments
UseofinvitroSystemstoElucidate
MitochondrialImportMechanisms
ProteinsareIncorporatedIntoMitochondria
ViaSeveralDifferentRoutes
Figure 12-23 Molecular Biology of the Cell (© Garland Science 2008)
Targe?ngtotheMatrixRequiresanNTerminalImportSequence
N-terminalImportSequencesFormAmphipathicα
HelicesthatInteractwiththeTom20/22Receptor
HydrophobiccleW
Figure 12-22 Molecular Biology of the Cell (© Garland Science 2008)
ProteinImportintotheMatrix
RequiresPassageThrough
TwoSeparateMembraneTranslocons
ProteinsTraversetheTOMandTIM
TransloconsinanUnfoldedState
Transloca?oninto
theMatrixOccursat
ZonesofAdhesion
ProteinImportintotheMatrixRequiresATP
HydrolysisandanIntactProtonGradient
AcrosstheInnerMembrane
Figure 12-26 Molecular Biology of the Cell (© Garland Science 2008)
Targe?ngtotheInnerMembraneOccursVia3Dis?nctRoutes
Stop-Transfer-Mediated Oxa1-Mediated
Single-Pass
Proteins
Cytochromeoxidase
subunitCoxVa
Tom70/Tim22/54-Mediated
Mul?-PassProteins
ADP/ATPAn?porter
ATPSynthaseSubunit9
Targe?ngtotheIntermembranous
SpaceOccursViaTwoDis?nctPathways
IMSpaceProtease
CytochromeB2
DirectDelivery
CytochromecHemeLyase
Targe?ngtotheOuterMembrane
ViatheSAMProteinComplex
(Sor3ngand
Assembly
Machinery)
(β-Barrell)
Figure 12-27 Molecular Biology of the Cell (© Garland Science 2008)
Nuclear
Transport
• Bidirec?onal
• SingleLargePoreComplex
Spans2lipidbilayers
• NuclearPoresmuchlarger
thanothertranslocons
Figure 12-8 Molecular Biology of the Cell (© Garland Science 2008)
EMofTransverseSec?onShowinga
Side-ViewthroughtwoNPCs
Figure 12-9c Molecular Biology of the Cell (© Garland Science 2008)
ScanningEMofNPCsasViewedfrom
theNucleoplasm
Figure 12-9b Molecular Biology of the Cell (© Garland Science 2008)
StructureofaNuclearPoreComplex
Figure 12-9a Molecular Biology of the Cell (© Garland Science 2008)
GatedDiffusionBarrierModelof
NuclearTransport
Meshworkofdisordered
proteindomains
containingFGrepeats
Figure 12-10 Molecular Biology of the Cell (© Garland Science 2008)
NuclearImportSignalsareHighly
DiverseinSequence
• Bindtodis?nctnuclearimportreceptors
• Canbeanywhereintheproteinsequence
butprobablyresideonsurfacepatches
• Somearenotyetiden?fied
Figure 12-11 Molecular Biology of the Cell (© Garland Science 2008)
GoldPar?clesCoatedwithPep?des
ContainingaNLSTraverseNPCs
Proteinsdonothavetobe
unfoldedbeforethey
traversethenuclearpore
Figure 12-12 Molecular Biology of the Cell (© Garland Science 2008)
NuclearImportandExportSequencesare
RecognizedbyDifferentMembersofthe
SameReceptorFamily(Keryopherins)
Figure 12-13 Molecular Biology of the Cell (© Garland Science 2008)
Direc?onalityisConferredonNuclearTransportbya
GradientofRan-GDP/GTPAcrosstheNuclearEnvelope
Figure 12-14 Molecular Biology of the Cell (© Garland Science 2008)
NuclearImportandExportOperateViaReciprocal
UseoftheRan-GDP/GTPConcentra?onGradient
Figure 12-15 Molecular Biology of the Cell (© Garland Science 2008)