2017
Neuronal Death After Hemorrhagic Stroke In Vitro and In Vivo Shares Features of Ferroptosis and Necroptosis
Zille M, Karuppagounder SS, Chen Y, Gough PJ, Bertin J, Finger J, Milner TA, Jonas EA, Ratan RR. Neuronal Death After Hemorrhagic Stroke In Vitro and In Vivo Shares Features of Ferroptosis and Necroptosis. Stroke 2017, 48: 1033-1043. PMID: 28250197, PMCID: PMC5613764, DOI: 10.1161/strokeaha.116.015609.Peer-Reviewed Original ResearchConceptsCell death mechanismsCaspase-dependent apoptosisDeath mechanismsMolecular markersChemical inhibitorsCell death pathwaysNecroptotic cell deathSecondary injuryNecroptotic signalingDeath pathwaysNecrotic phenotypeIntracerebral hemorrhageCell deathMRNA synthesisNecroptosisIntracerebral hemorrhage (ICH) resultsShare featuresFerroptosisHemin-induced toxicityFerroptosis inhibitorsAutophagyCultured neuronsApoptosisHemorrhage resultsNeuronal necrosis
2016
The Mitochondrial Permeability Transition Pore and ATP Synthase
Beutner G, Alavian K, Jonas EA, Porter GA. The Mitochondrial Permeability Transition Pore and ATP Synthase. Handbook Of Experimental Pharmacology 2016, 240: 21-46. PMID: 27590224, PMCID: PMC7439278, DOI: 10.1007/164_2016_5.BooksConceptsPermeability transition poreElectron transport chainATP synthaseGeneration of ATPMitochondrial permeability transition poreATP generationTransition poreCell deathC subunit ringMitochondrial ATP generationFo subunitsEmbryonic mouse heartPTP openingTransport chainOxidative phosphorylationEquivalents NADHMature cellsSynthasePhysiologic roleMouse heartsATPRecent studiesPhosphorylationSubunitsFADH2
2013
PINK1 protects against cell death induced by mitochondrial depolarization, by phosphorylating Bcl-xL and impairing its pro-apoptotic cleavage
Arena G, Gelmetti V, Torosantucci L, Vignone D, Lamorte G, De Rosa P, Cilia E, Jonas EA, Valente EM. PINK1 protects against cell death induced by mitochondrial depolarization, by phosphorylating Bcl-xL and impairing its pro-apoptotic cleavage. Cell Death & Differentiation 2013, 20: 920-930. PMID: 23519076, PMCID: PMC3679455, DOI: 10.1038/cdd.2013.19.Peer-Reviewed Original ResearchConceptsBcl-xLMitochondrial depolarizationCell deathPro-autophagic protein Beclin-1Autosomal recessive Parkinson's diseaseBeclin-1Recessive Parkinson's diseaseAnti-apoptotic proteinsXL interactionMitochondrial kinaseProtein Beclin 1Mitochondrial traffickingMitochondrial homeostasisMitophagy pathwayBcl-xL.PINK1Functional linkCell survivalPathogenesis of PDNovel mechanismPINK1 genePathwayCleavageMitophagyParkinson's disease
2012
Multipolar functions of BCL-2 proteins link energetics to apoptosis
Hardwick JM, Chen YB, Jonas EA. Multipolar functions of BCL-2 proteins link energetics to apoptosis. Trends In Cell Biology 2012, 22: 318-328. PMID: 22560661, PMCID: PMC3499971, DOI: 10.1016/j.tcb.2012.03.005.Peer-Reviewed Original ResearchConceptsBcl-2 proteinClassical apoptotic cell deathBcl-2 family proteinsSub-mitochondrial localizationApoptotic cell deathFamily proteinsClassical apoptosisBiochemical activityApoptosis regulatorCritical crosstalkCell survivalCell deathProteinApoptosisProfound effectCellsMultipolar functionsRegulatorCrosstalkLocalizationCurrent assumptionsDeath
2009
Molecular participants in mitochondrial cell death channel formation during neuronal ischemia
Jonas EA. Molecular participants in mitochondrial cell death channel formation during neuronal ischemia. Experimental Neurology 2009, 218: 203-212. PMID: 19341732, PMCID: PMC2710418, DOI: 10.1016/j.expneurol.2009.03.025.Peer-Reviewed Original ResearchConceptsBcl-2 family proteinsCell deathFamily proteinsInner membraneOuter membraneIon channelsMolecular participantsNumerous cellular processesMitochondrial ion channelsComplex of proteinsSpecialized physiological functionsMembrane compartmentalizationIon channel complexCellular processesPhysiological functionsIon channel conductanceCytosolic metabolitesChannel complexProteinMembrane potentialChannel formationMembraneChannel conductanceSynaptic transmissionVDACBcl-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 hDIABLOMitochondriaAktTranslocationBcl
2006
Mitochondrial factors with dual roles in death and survival
Cheng WC, Berman SB, Ivanovska I, Jonas EA, Lee SJ, Chen Y, Kaczmarek LK, Pineda F, Hardwick JM. Mitochondrial factors with dual roles in death and survival. Oncogene 2006, 25: 4697-4705. PMID: 16892083, DOI: 10.1038/sj.onc.1209596.Peer-Reviewed Original ResearchConceptsBcl-2 family proteinsCell deathCell death regulatorsPro-death Bcl-2 family proteinNormal cellular functionMitochondrial fission proteinDeath regulatorsDeath stimuliCellular functionsFamily proteinsMitochondrial factorsFission proteinsCell survivalBiochemical mechanismsCaspasesDual roleProteinHealthy cellsCellsMammalsMitochondriaRegulatorSurvivalDeathStretchBCL-xL regulates synaptic plasticity.
Jonas E. BCL-xL regulates synaptic plasticity. Molecular Interventions 2006, 6: 208-22. PMID: 16960143, DOI: 10.1124/mi.6.4.7.Peer-Reviewed Original ResearchConceptsBcl-xLSynaptic vesicle recyclingRole of mitochondriaHigh synaptic activityMembrane ion pumpsMitochondrial localizationCalcium homeostasisVesicle recyclingPresynaptic terminalsPredominant organellesCell deathSynaptic vesiclesSynaptic developmentIon pumpsIntracellular calcium homeostasisRecent discoveryMitochondriaSynaptic transmitter releaseHomeostasisSynaptic plasticitySynaptic sitesSynapseSynaptic processesSynaptic activityOrganelles
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 releaseThe Role of the Mitochondrial Apoptosis Induced Channel MAC in Cytochrome c Release
Martinez-Caballero S, Dejean LM, Jonas EA, Kinnally KW. The Role of the Mitochondrial Apoptosis Induced Channel MAC in Cytochrome c Release. Journal Of Bioenergetics And Biomembranes 2005, 37: 155-164. PMID: 16167172, DOI: 10.1007/s10863-005-6570-z.Peer-Reviewed Original ResearchConceptsMitochondrial apoptosis-induced channelBcl-2 family proteinsMitochondrial outer membraneCytochrome cOuter membrane integrityCytochrome c releaseHigh-conductance channelPermeability transition poreIntermembrane spaceFamily proteinsCommitment stepOuter membraneC releaseProapoptotic factorsTransition poreSingle-channel behaviorMAC formationMembrane integrityCrucial eventEarly apoptosisApoptosisMolecular compositionRelease channelMAC activityMitochondriaOligomeric Bax Is a Component of the Putative Cytochrome c Release Channel MAC, Mitochondrial Apoptosis-induced Channel
Dejean LM, Martinez-Caballero S, Guo L, Hughes C, Teijido O, Ducret T, Ichas F, Korsmeyer SJ, Antonsson B, Jonas EA, Kinnally KW. Oligomeric Bax Is a Component of the Putative Cytochrome c Release Channel MAC, Mitochondrial Apoptosis-induced Channel. Molecular Biology Of The Cell 2005, 16: 2424-2432. PMID: 15772159, PMCID: PMC1087246, DOI: 10.1091/mbc.e04-12-1111.Peer-Reviewed Original ResearchConceptsMitochondrial apoptosis-induced channelOligomeric BaxBcl-2 family proteinsHeLa cellsBcl-2-overexpressing cellsCytochrome cChannel activityMAC activityIntrinsic apoptotic pathwayApoptotic cellsFamily proteinsIntrinsic apoptosisApoptotic pathwaySingle-channel behaviorMitochondriaBaxBax antibodiesMean conductanceBakUntreated cellsRelease channelProteinApoptosisCellsTranslocation
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
BAK Alters Neuronal Excitability and Can Switch from Anti- to Pro-Death Function during Postnatal Development
Fannjiang Y, Kim CH, Huganir RL, Zou S, Lindsten T, Thompson CB, Mito T, Traystman RJ, Larsen T, Griffin DE, Mandir AS, Dawson TM, Dike S, Sappington AL, Kerr DA, Jonas EA, Kaczmarek LK, Hardwick JM. BAK Alters Neuronal Excitability and Can Switch from Anti- to Pro-Death Function during Postnatal Development. Developmental Cell 2003, 4: 575-585. PMID: 12689595, DOI: 10.1016/s1534-5807(03)00091-1.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsAnimals, NewbornApoptosisBcl-2 Homologous Antagonist-Killer ProteinCentral Nervous SystemCentral Nervous System DiseasesCentral Nervous System Viral DiseasesDisease Models, AnimalEpilepsyExcitatory Postsynaptic PotentialsGenetic VectorsHippocampusKainic AcidMaleMembrane ProteinsMiceMice, KnockoutNeurodegenerative DiseasesNeuronsNeurotoxinsProtein Structure, TertiarySindbis VirusStrokeSynaptic TransmissionConceptsNeuronal excitabilityVirus infectionPostnatal developmentAlters neuronal excitabilityKainate-induced seizuresSpinal cord neuronsIschemia/strokeSindbis virus infectionNeuronal injuryCord neuronsNeuronal deathProtective effectSynaptic activityMouse modelParkinson's diseaseNeuron subtypesNeurotransmitter releasePro-death functionMiceNeuronsSpecific death stimuliDeathSeizuresPossible roleExcitability