2011
Bcl-xL regulates mitochondrial energetics by stabilizing the inner membrane potential
Chen YB, Aon MA, Hsu YT, Soane L, Teng X, McCaffery JM, Cheng WC, Qi B, Li H, Alavian KN, Dayhoff-Brannigan M, Zou S, Pineda FJ, O'Rourke B, Ko YH, Pedersen PL, Kaczmarek LK, Jonas EA, Hardwick JM. Bcl-xL regulates mitochondrial energetics by stabilizing the inner membrane potential. Journal Of Cell Biology 2011, 195: 263-276. PMID: 21987637, PMCID: PMC3198165, DOI: 10.1083/jcb.201108059.Peer-Reviewed Original ResearchConceptsMitochondrial membrane potentialMitochondrial membraneMitochondrial ATP synthase β-subunitATP synthase β subunitBcl-2 family proteinsOuter membrane permeabilizationInner mitochondrial membrane potentialMembrane potentialMitochondrial energetic capacityOuter mitochondrial membraneSynthase β subunitInner mitochondrial membraneInner membrane potentialATP synthaseFamily proteinsBiochemical approachesGenetic evidenceEndogenous BclMembrane permeabilizationCellular resourcesΒ-subunitBcl-xLMitochondrial energeticsEnergetic capacityMitochondrial cristae
2007
Bcl-xL Inhibitor ABT-737 Reveals a Dual Role for Bcl-xL in Synaptic Transmission
Hickman JA, Hardwick JM, Kaczmarek LK, Jonas EA. Bcl-xL Inhibitor ABT-737 Reveals a Dual Role for Bcl-xL in Synaptic Transmission. Journal Of Neurophysiology 2007, 99: 1515-1522. PMID: 18160428, PMCID: PMC2836590, DOI: 10.1152/jn.00598.2007.Peer-Reviewed Original ResearchConceptsMitochondrial outer membraneEndogenous Bcl-xLMitochondrial channel activityBcl-xLInhibitor ABT-737ABT-737Outer membraneBcl-xL.Pro-apoptotic cleavage productRecombinant Bcl-xLChannel activityBcl-xL proteinSynaptic functionDual roleGenetic toolsDomain pocketSynaptic transmissionSynaptic activityGiant presynaptic terminalEquivalent modificationEndogenous proteolysisRepetitive synaptic activityBH3Cleavage productsProtein
2005
Actions of BAX on Mitochondrial Channel Activity and on Synaptic Transmission
Jonas EA, Hardwick JM, Kaczmarek LK. Actions of BAX on Mitochondrial Channel Activity and on Synaptic Transmission. Antioxidants & Redox Signaling 2005, 7: 1092-1100. PMID: 16115013, DOI: 10.1089/ars.2005.7.1092.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBcl-2-Associated X ProteinBcl-X ProteinCell MembraneElectrophysiologyIntracellular MembranesLiposomesLoligoMitochondriaMultigene FamilyNeurotransmitter AgentsPatch-Clamp TechniquesPeptidesPresynaptic TerminalsProtein Structure, TertiarySynapsesSynaptic TransmissionTime FactorsConceptsMitochondrial membraneBcl-2 family proteins BaxCell deathOuter mitochondrial membraneAction of BaxMitochondrial channel activityChannel activityNormal physiological settingsAntiapoptotic Bcl-xL proteinBcl-xL proteinDeath channelMitochondrial architectureMitochondrial channelsProapoptotic fragmentsLarge conductance channelPresynaptic terminalsBcl-xL.Proapoptotic proteinsAlternative functionsProtein BaxPhysiological settingsPhysiological roleSynaptic transmissionBaxNeurotransmitter release
2004
Exposure to Hypoxia Rapidly Induces Mitochondrial Channel Activity within a Living Synapse*
Jonas EA, Hickman JA, Hardwick JM, Kaczmarek LK. Exposure to Hypoxia Rapidly Induces Mitochondrial Channel Activity within a Living Synapse*. Journal Of Biological Chemistry 2004, 280: 4491-4497. PMID: 15561723, DOI: 10.1074/jbc.m410661200.Peer-Reviewed Original ResearchConceptsMitochondrial channel activityMitochondrial membraneChannel activityBcl-xLBcl-2 family proteinsPro-apoptotic fragmentsOuter mitochondrial membraneTrigger cell deathZ-VAD-FMKBenzyloxycarbonyl-VADFamily proteinsSynaptic responsesMulticonductance channelLarge conductance channelFluoromethyl ketoneCell deathMinutes of hypoxiaResponses of neuronsNeuronal functionSquid giant synapseSynaptic mitochondriaEarly eventsSynaptic functionHypoxic conditionsNeuronal deathProapoptotic N-truncated BCL-xL protein activates endogenous mitochondrial channels in living synaptic terminals
Jonas EA, Hickman JA, Chachar M, Polster BM, Brandt TA, Fannjiang Y, Ivanovska I, Basañez G, Kinnally KW, Zimmerberg J, Hardwick JM, Kaczmarek LK. Proapoptotic N-truncated BCL-xL protein activates endogenous mitochondrial channels in living synaptic terminals. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 13590-13595. PMID: 15342906, PMCID: PMC518799, DOI: 10.1073/pnas.0401372101.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBcl-X ProteinDecapodiformesElectric ConductivityEndopeptidasesHypoxiaIon ChannelsLiposomesMitochondriaNADPatch-Clamp TechniquesPorinsPresynaptic TerminalsProtein Processing, Post-TranslationalProto-Oncogene Proteins c-bcl-2Sequence DeletionVoltage-Dependent Anion ChannelsConceptsBcl-xLMitochondrial channelsDeath pathwaysMitochondrial membraneBcl-xL.Proapoptotic Bcl-2 family proteinsVoltage-dependent anion channelBcl-2 family proteinsOuter mitochondrial membraneCell death pathwaysHydrophobic C-terminusBcl-xL proteinAntiapoptotic Bcl-xLNeuronal death pathwaysDeath stimuliBH3 domainFamily proteinsSquid presynaptic terminalsMammalian cellsC-terminusAnion channelMitochondriaChannel activityOpposite effectHealthy neurons
2003
Modulation of Synaptic Transmission by the BCL-2 Family Protein BCL-xL
Jonas EA, Hoit D, Hickman JA, Brandt TA, Polster BM, Fannjiang Y, McCarthy E, Montanez MK, Hardwick JM, Kaczmarek LK. Modulation of Synaptic Transmission by the BCL-2 Family Protein BCL-xL. Journal Of Neuroscience 2003, 23: 8423-8431. PMID: 12968005, PMCID: PMC6740692, DOI: 10.1523/jneurosci.23-23-08423.2003.Peer-Reviewed Original ResearchConceptsBcl-2 family proteinsProtein Bcl-xLBcl-xLFamily proteinsMitochondrial membranePro-apoptotic cleavage productRecombinant Bcl-xLBcl-xL proteinMitochondrial calcium uptakePresynaptic terminalsInfluences synaptic transmissionCell deathGiant presynaptic terminalSynaptic transmissionChannel activityProteinSquid stellate ganglionMitochondriaCleavage productsSynaptic stabilityAdult brainPostsynaptic responsesCalcium uptakeMembranePatch pipette