2022
Alpha-tocotrienol enhances arborization of primary hippocampal neurons via upregulation of Bcl-xL
Park HA, Crowe-White KM, Ciesla L, Scott M, Bannerman S, Davis AU, Adhikari B, Burnett G, Broman K, Ferdous KA, Lackey KH, Licznerski P, Jonas EA. Alpha-tocotrienol enhances arborization of primary hippocampal neurons via upregulation of Bcl-xL. Nutrition Research 2022, 101: 31-42. PMID: 35366596, PMCID: PMC9081260, DOI: 10.1016/j.nutres.2022.02.007.Peer-Reviewed Original ResearchConceptsPrimary hippocampal neuronsControl neuronsHippocampal neuronsAlpha-tocotrienolBcl-xLVitamin E familyCerebral ischemiaNeuronal viabilityMature neuronsB cellsNeurite complexityNeuronal functionMitochondrial energy productionBrain developmentCentral mechanismsNeuronsBeneficial effectsOxidative stressBcl-xL upregulationProtein levelsNeurite branchingTreatmentE familyATP levelsNeurite outgrowth
2019
Alpha-Tocotrienol Prevents Oxidative Stress-Mediated Post-Translational Cleavage of Bcl-xL in Primary Hippocampal Neurons
Park HA, Mnatsakanyan N, Broman K, Davis AU, May J, Licznerski P, Crowe-White KM, Lackey KH, Jonas EA. Alpha-Tocotrienol Prevents Oxidative Stress-Mediated Post-Translational Cleavage of Bcl-xL in Primary Hippocampal Neurons. International Journal Of Molecular Sciences 2019, 21: 220. PMID: 31905614, PMCID: PMC6982044, DOI: 10.3390/ijms21010220.Peer-Reviewed Original ResearchConceptsPrimary hippocampal neuronsHippocampal neuronsReactive oxygen speciesMitochondrial dysfunctionBcl-xLMitochondrial membrane potentialMitochondrial functionProduction of ROSExcitotoxic conditionsGlutamate challengeNeuroprotective propertiesMembrane potentialNeuronal deathExcitotoxic stimulationBcl-xL levelsNeuronal survivalIntracellular ATP depletionMitochondrial reactive oxygen speciesB cellsImportant causeDysfunctionNeuronsROS productionATP depletionNeurite outgrowthThe mitochondrial metabolic function of DJ‐1 is modulated by 14‐3‐3β
Weinert M, Millet A, Jonas EA, Alavian KN. The mitochondrial metabolic function of DJ‐1 is modulated by 14‐3‐3β. The FASEB Journal 2019, 33: 8925-8934. PMID: 31034784, PMCID: PMC6988861, DOI: 10.1096/fj.201802754r.Peer-Reviewed Original ResearchConceptsMitochondrial metabolic efficiencyMitochondrial metabolic functionDisease genesMetabolic efficiencyMetabolic functionsMajor signaling pathwaysNovel molecular mechanismHypoxia-dependent mannerParkinson's disease genesKey adaptive mechanismsMitochondrial plasticityChaperone activityCellular metabolic demandsMetabolic plasticityReactive oxygen speciesMolecular mechanismsOxidative phosphorylationPleiotropic functionsSignaling pathwaysDJ-1Cell survivalCancer cellsOxygen speciesAdaptive mechanismsPathophysiological conditions
2015
Bcl-xL Is Necessary for Neurite Outgrowth in Hippocampal Neurons
Park HA, Licznerski P, Alavian KN, Shanabrough M, Jonas EA. Bcl-xL Is Necessary for Neurite Outgrowth in Hippocampal Neurons. Antioxidants & Redox Signaling 2015, 22: 93-108. PMID: 24787232, PMCID: PMC4281845, DOI: 10.1089/ars.2013.5570.Peer-Reviewed Original ResearchConceptsDeath receptor 6Hippocampal neuronsNeurite outgrowthExacerbation of hypoxiaBcl-xLNeuronal outgrowthNeuronal process outgrowthNeuronal injuryNeurodegenerative stimuliVivo ischemiaHypoxic injuryNeuronal survivalBrain injuryImpairs neurite outgrowthHypoxic controlsSynapse numberAxonal pruningNeurite damageB cellsReceptor 6Synaptic plasticityDR6 expressionSynapse formationEarly increaseNeurons
2014
An uncoupling channel within the c-subunit ring of the F1FO ATP synthase is the mitochondrial permeability transition pore
Alavian KN, Beutner G, Lazrove E, Sacchetti S, Park HA, Licznerski P, Li H, Nabili P, Hockensmith K, Graham M, Porter GA, Jonas EA. An uncoupling channel within the c-subunit ring of the F1FO ATP synthase is the mitochondrial permeability transition pore. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 10580-10585. PMID: 24979777, PMCID: PMC4115574, DOI: 10.1073/pnas.1401591111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCell DeathHEK293 CellsHumansIon Channel GatingIon ChannelsLiposomesMitochondriaMitochondrial Membrane Transport ProteinsMitochondrial MembranesMitochondrial Permeability Transition PoreMutationProtein ConformationProtein SubunitsProton-Translocating ATPasesRatsReactive Oxygen SpeciesConceptsMitochondrial PT poreF1Fo-ATP synthaseATP synthasePermeability transitionCell deathCellular metabolic efficiencyInner mitochondrial membrane permeabilityOxygen species-induced cell deathC subunit ringATP synthase F1Mitochondrial membrane permeabilityMitochondrial permeability transitionC subunitPT poreTight regulationATP productionMolecular identitySingle-channel conductanceChannel closureLeak channelsMPTP openingMetabolic efficiencyMembrane permeabilityHealthy cellsOsmotic shifts
2013
A Bcl-xL–Drp1 complex regulates synaptic vesicle membrane dynamics during endocytosis
Li H, Alavian KN, Lazrove E, Mehta N, Jones A, Zhang P, Licznerski P, Graham M, Uo T, Guo J, Rahner C, Duman RS, Morrison RS, Jonas EA. A Bcl-xL–Drp1 complex regulates synaptic vesicle membrane dynamics during endocytosis. Nature Cell Biology 2013, 15: 773-785. PMID: 23792689, PMCID: PMC3725990, DOI: 10.1038/ncb2791.Peer-Reviewed Original ResearchConceptsBcl-xLVesicle retrievalProtein-protein interactionsClathrin-coated pitsProtein Bcl-xLCalmodulin-dependent mannerRecruitment of vesiclesNeurotransmitter releaseDepletion of Drp1GTPase Drp1Vesicle endocytosisEndocytic vesiclesMembrane dynamicsPlasma membraneClathrin complexMutagenesis studiesPresynaptic plasticityMitochondrial ATPATP availabilityReserve poolDrp1EndocytosisVesiclesHippocampal neuronsComplexesF1FO ATPase vesicle preparation and technique for performing patch clamp recordings of submitochondrial vesicle membranes.
Sacchetti S, Alavian KN, Lazrove E, Jonas EA. F1FO ATPase vesicle preparation and technique for performing patch clamp recordings of submitochondrial vesicle membranes. Journal Of Visualized Experiments 2013, e4394. PMID: 23685483, PMCID: PMC3676267, DOI: 10.3791/4394.Peer-Reviewed Original ResearchConceptsF1Fo-ATP synthaseATP synthaseF1Fo-ATPaseSubmitochondrial vesiclesNecrotic cell deathPro-apoptotic factorsCell deathOuter membraneBcl-2 family proteinsMitochondrial outer membraneImportant cellular functionsOuter membrane ruptureImportant mitochondrial functionsRole of mitochondriaMediation of signalsMitochondrial permeability transition poreProduction of ATPApoptotic cell deathPermeability transition poreInner membrane poreCellular functionsFamily proteinsInner membraneOxidative phosphorylationBeta subunit
2012
NAD kinase regulates the size of the NADPH pool and insulin secretion in pancreatic β-cells
Gray JP, Alavian KN, Jonas EA, Heart EA. NAD kinase regulates the size of the NADPH pool and insulin secretion in pancreatic β-cells. AJP Endocrinology And Metabolism 2012, 303: e191-e199. PMID: 22550069, PMCID: PMC3431206, DOI: 10.1152/ajpendo.00465.2011.Peer-Reviewed Original ResearchConceptsGlucose-stimulated insulin secretionInsulin secretionΒ-cellsPancreatic β-cellsRedox cycling agent menadioneRat β-cell lineΒ-cell lineINS-1 832/13 cellsTwo- to threefold increaseAntioxidant defense systemRodent isletsSecretionGlucose concentrationOxidative damageOxidative defenseThreefold increaseNADPH/Cytosolic reductasesAgent menadioneN-terminally cleaved Bcl-xL mediates ischemia-induced neuronal death
Ofengeim D, Chen YB, Miyawaki T, Li H, Sacchetti S, Flannery RJ, Alavian KN, Pontarelli F, Roelofs BA, Hickman JA, Hardwick JM, Zukin RS, Jonas EA. N-terminally cleaved Bcl-xL mediates ischemia-induced neuronal death. Nature Neuroscience 2012, 15: 574-580. PMID: 22366758, PMCID: PMC3862259, DOI: 10.1038/nn.3054.Peer-Reviewed Original ResearchEffects of dexpramipexole on brain mitochondrial conductances and cellular bioenergetic efficiency
Alavian KN, Dworetzky SI, Bonanni L, Zhang P, Sacchetti S, Mariggio MA, Onofrj M, Thomas A, Li H, Mangold JE, Signore AP, DeMarco U, Demady DR, Nabili P, Lazrove E, Smith PJ, Gribkoff VK, Jonas EA. Effects of dexpramipexole on brain mitochondrial conductances and cellular bioenergetic efficiency. Brain Research 2012, 1446: 1-11. PMID: 22364637, PMCID: PMC3746080, DOI: 10.1016/j.brainres.2012.01.046.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAdrenergic beta-AntagonistsAnalysis of VarianceAnimalsBiophysical PhenomenaBrainCell SurvivalCells, CulturedCyclosporineDose-Response Relationship, DrugEnergy MetabolismEnzyme InhibitorsHumansMaleMembrane Potential, MitochondrialMiceMitochondriaMitochondrial MembranesNeuroblastomaNeuronsOligopeptidesOxygen ConsumptionPatch-Clamp TechniquesPropranololRatsRats, Sprague-DawleyConceptsAmyotrophic lateral sclerosisParkinson's diseaseRisk of deathChronic neurological disorderLateral sclerosisInefficient energy productionNeurological disordersMitochondrial dysfunctionMembrane currentsDiseaseCellular energy productionDysfunctional mitochondriaCellular stressSclerosisDysfunctionDexpramipexoleInjuryNeurons
2011
Bcl-xL regulates metabolic efficiency of neurons through interaction with the mitochondrial F1FO ATP synthase
Alavian KN, Li H, Collis L, Bonanni L, Zeng L, Sacchetti S, Lazrove E, Nabili P, Flaherty B, Graham M, Chen Y, Messerli SM, Mariggio MA, Rahner C, McNay E, Shore GC, Smith PJ, Hardwick JM, Jonas EA. Bcl-xL regulates metabolic efficiency of neurons through interaction with the mitochondrial F1FO ATP synthase. Nature Cell Biology 2011, 13: 1224-1233. PMID: 21926988, PMCID: PMC3186867, DOI: 10.1038/ncb2330.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsBcl-2 Homologous Antagonist-Killer ProteinBcl-2-Associated X ProteinBcl-X ProteinBiphenyl CompoundsCarbonyl Cyanide p-TrifluoromethoxyphenylhydrazoneCells, CulturedEnergy MetabolismEnzyme InhibitorsHippocampusHydrolysisMembrane Potential, MitochondrialMitochondriaMitochondrial MembranesMitochondrial Proton-Translocating ATPasesNeuronsNitrophenolsOligomycinsOxygen ConsumptionPatch-Clamp TechniquesPiperazinesProton IonophoresRatsRecombinant Fusion ProteinsRNA InterferenceSulfonamidesSynapsesTime FactorsTransfectionConceptsBcl-xLSynthase complexATP synthaseMitochondrial F1Fo-ATP synthaseAnti-apoptotic BCL2 family proteinsF1Fo-ATP synthaseATP synthase complexF1FO-ATPase activityBcl-xL activityATPase activityBcl-xL proteinBCL2 family proteinsEndogenous Bcl-xLPresence of ATPFamily proteinsATPase complexNormal neuronal functionMembrane leak conductanceSubmitochondrial vesiclesΒ-subunitProtect cellsGenetic inhibitionMitochondrial efficiencyF1FoApoptotic molecules
2009
Bcl-xL increases mitochondrial fission, fusion, and biomass in neurons
Berman SB, Chen YB, Qi B, McCaffery JM, Rucker EB, Goebbels S, Nave KA, Arnold BA, Jonas EA, Pineda FJ, Hardwick JM. Bcl-xL increases mitochondrial fission, fusion, and biomass in neurons. Journal Of Cell Biology 2009, 184: 707-719. PMID: 19255249, PMCID: PMC2686401, DOI: 10.1083/jcb.200809060.Peer-Reviewed Original ResearchConceptsMitochondrial fissionMitochondrial morphologyCell deathApoptotic cell deathRate of fissionMitochondrial organellesOrganelle morphologyMitochondrial biomassBcl-xLCell typesFluorescence microscopyHealthy neuronsBclCultured neuronsDependent mechanismNeuronal dysfunctionFissionNeuronal processesBiomassSynaptic activityFusionOrganellesComputational strategyRate of fusionRegulation
2008
Ischemic preconditioning blocks BAD translocation, Bcl-xL cleavage, and large channel activity in mitochondria of postischemic hippocampal neurons
Miyawaki T, Mashiko T, Ofengeim D, Flannery RJ, Noh KM, Fujisawa S, Bonanni L, Bennett MV, Zukin RS, Jonas EA. Ischemic preconditioning blocks BAD translocation, Bcl-xL cleavage, and large channel activity in mitochondria of postischemic hippocampal neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 4892-4897. PMID: 18347331, PMCID: PMC2290755, DOI: 10.1073/pnas.0800628105.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBcl-Associated Death ProteinBcl-X ProteinBrain IschemiaCaspase InhibitorsChromonesHippocampusIon Channel GatingIschemic PreconditioningLarge-Conductance Calcium-Activated Potassium ChannelsMaleMitochondriaMorpholinesNeuronsPhosphoinositide-3 Kinase InhibitorsPhosphorylationProtein TransportProto-Oncogene Proteins c-aktRatsRats, Sprague-DawleySignal TransductionConceptsMitochondrial outer membraneSmac/DIABLOPI3K/AktOuter membraneCytochrome cFeatures of apoptosisSpecific PI3K inhibitor LY294002PI3K inhibitor LY294002K inhibitor LY294002Mitochondrial translocationMitochondrial releaseMitochondrial membraneVulnerable CA1 pyramidal cellsLarge conductance channelBad translocationInhibitor LY294002PI3KNeuronal deathChannel activityVivo 1 hDIABLOMitochondriaAktTranslocationBclBcl-xL induces Drp1-dependent synapse formation in cultured hippocampal neurons
Li H, Chen Y, Jones AF, Sanger RH, Collis LP, Flannery R, McNay EC, Yu T, Schwarzenbacher R, Bossy B, Bossy-Wetzel E, Bennett MV, Pypaert M, Hickman JA, Smith PJ, Hardwick JM, Jonas EA. Bcl-xL induces Drp1-dependent synapse formation in cultured hippocampal neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 2169-2174. PMID: 18250306, PMCID: PMC2542873, DOI: 10.1073/pnas.0711647105.Peer-Reviewed Original ResearchConceptsBcl-xL proteinBcl-xLVesicle clustersDynamin-related protein 1Synapse formationOverexpression of Drp1Mitochondrial fission proteinSynaptic vesicle clustersMitochondrial localizationFission proteinsGTPase activityDrp1Cultured hippocampal neuronsMitochondrial functionHippocampal neuronsNeuronal synapsesRecombinant systemsABT-737Protein 1ProteinTissue lysatesAdult neuronsSpontaneous miniature synaptic currentsOverexpressionMiniature synaptic currents
2006
Zinc-Dependent Multi-Conductance Channel Activity in Mitochondria Isolated from Ischemic Brain
Bonanni L, Chachar M, Jover-Mengual T, Li H, Jones A, Yokota H, Ofengeim D, Flannery RJ, Miyawaki T, Cho CH, Polster BM, Pypaert M, Hardwick JM, Sensi SL, Zukin RS, Jonas EA. Zinc-Dependent Multi-Conductance Channel Activity in Mitochondria Isolated from Ischemic Brain. Journal Of Neuroscience 2006, 26: 6851-6862. PMID: 16793892, PMCID: PMC4758341, DOI: 10.1523/jneurosci.5444-05.2006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternBrain IschemiaCaspasesChelating AgentsDiagnostic ImagingDose-Response Relationship, DrugEthylenediaminesIon Channel GatingIon ChannelsMaleMembrane PotentialsMicroscopy, Electron, TransmissionMitochondriaNADPatch-Clamp TechniquesRatsRats, Sprague-DawleySynaptosomesXanthenesZinc
2003
Modulation of mitochondrial function by endogenous Zn2+ pools
Sensi SL, Ton-That D, Sullivan PG, Jonas EA, Gee KR, Kaczmarek LK, Weiss JH. Modulation of mitochondrial function by endogenous Zn2+ pools. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 6157-6162. PMID: 12724524, PMCID: PMC156342, DOI: 10.1073/pnas.1031598100.Peer-Reviewed Original ResearchConceptsDirect patch-clamp recordingsCultured cortical neuronsPatch-clamp recordingsCertain brain regionsNeuronal injuryPool of intracellularCortical neuronsIntact neuronsReactive oxygen species generationPostsynaptic neuronsClamp recordingsSynaptic spacePotent effectsBrain regionsOxygen species generationBrain mitochondriaMitochondrial poolMembrane depolarizationNeuronsRecent evidenceFurther studiesMitochondrial functionROS generationNovel evidenceSpecies generation