2022
Mitochondrial ATP synthase c-subunit leak channel triggers cell death upon loss of its F1 subcomplex
Mnatsakanyan N, Park HA, Wu J, He X, Llaguno MC, Latta M, Miranda P, Murtishi B, Graham M, Weber J, Levy RJ, Pavlov EV, Jonas EA. Mitochondrial ATP synthase c-subunit leak channel triggers cell death upon loss of its F1 subcomplex. Cell Death & Differentiation 2022, 29: 1874-1887. PMID: 35322203, PMCID: PMC9433415, DOI: 10.1038/s41418-022-00972-7.Peer-Reviewed Original ResearchConceptsMitochondrial permeability transitionATP synthase c-subunitCell deathMitochondrial ATP synthaseChannel activityCellular energy productionLeak channelsVoltage-gated ion channelsF1 subcomplexATP synthaseC subunitInner membraneProkaryotic hostsCell stressPermeability transitionIon channelsGating mechanismOsmotic changesLarge conductanceC-ringChannels triggersNeuronal deathF1SubcomplexOsmotic gradient
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 outgrowthVitamin E Prevents ΔN-Bcl-xL-associate Mitochondrial Dysfunction in Primary Hippocampal Neurons (P14-024-19)
Park H, Mnatsakanyan N, Broman K, Jonas E. Vitamin E Prevents ΔN-Bcl-xL-associate Mitochondrial Dysfunction in Primary Hippocampal Neurons (P14-024-19). Current Developments In Nutrition 2019, 3: nzz052.p14-024-19. PMCID: PMC6574370, DOI: 10.1093/cdn/nzz052.p14-024-19.Peer-Reviewed Original ResearchBcl-xL.Bcl-xLPrimary hippocampal neuronsMitochondrial dysfunctionRedox statusBcl-xL protein levelsCaspase-dependent cleavageAnti-apoptotic Bcl-xLMitochondrial redox statusPro-survival proteinsNeuronal deathMitochondrial oxidative stressHippocampal neuronsOxidative stressReactive oxygen species formationMitochondrial membraneCaspase activitySubsequent oxidative stressMitochondrial potentialMitochondrial functionNeuronal energy metabolismOxygen species formationDependent cleavageOxidative stress productionEnergy metabolism
2017
ΔN-Bcl-xL, a therapeutic target for neuroprotection
Park HA, Jonas EA. ΔN-Bcl-xL, a therapeutic target for neuroprotection. Neural Regeneration Research 2017, 12: 1791-1794. PMID: 29239317, PMCID: PMC5745825, DOI: 10.4103/1673-5374.219033.Peer-Reviewed Original ResearchΔN-BclNeuronal deathNeuronal viabilityMitochondrial dysfunctionPrimary hippocampal neuronsABT-737Excitotoxic injuryGlutamate toxicityHippocampal neuronsAnti-apoptotic proteinsTherapeutic targetB cellsPrimary neuronsNeuronal functionAcute productionNeuroprotectionAltered metabolismMitochondrial damageNeuronsCentral targetMitochondrial functionDysfunctionDeathMitochondrial anti-apoptotic proteinDependent effects
2014
Bcl-xL in neuroprotection and plasticity
Jonas EA, Porter GA, Alavian KN. Bcl-xL in neuroprotection and plasticity. Frontiers In Physiology 2014, 5: 355. PMID: 25278904, PMCID: PMC4166110, DOI: 10.3389/fphys.2014.00355.BooksMitochondrial outer membrane permeabilizationBcl-xLSynapse formationOuter membrane permeabilizationMaster regulator proteinBcl-2 family member Bcl-xLPro-death factorsPro-apoptotic factorsNeurodegenerative diseasesVesicular traffickingSpecialized proteinsRegulator proteinMembrane permeabilizationCell stressBioenergetic efficiencyHigh metabolic demandsNeurodegenerative stimuliProteinNormal neuronal activityChannel activityNeuronal functionGenetic mutationsSuch protective strategiesNeuroprotective strategiesNeuronal death
2012
N-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 Research
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
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 death
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