2020
Inefficient thermogenic mitochondrial respiration due to futile proton leak in a mouse model of fragile X syndrome
Griffiths KK, Wang A, Wang L, Tracey M, Kleiner G, Quinzii CM, Sun L, Yang G, Perez‐Zoghbi J, Licznerski P, Yang M, Jonas EA, Levy RJ. Inefficient thermogenic mitochondrial respiration due to futile proton leak in a mouse model of fragile X syndrome. The FASEB Journal 2020, 34: 7404-7426. PMID: 32307754, PMCID: PMC7692004, DOI: 10.1096/fj.202000283rr.Peer-Reviewed Original ResearchConceptsFragile X syndromeProton leakMental retardation protein (FMRP) expressionInefficient oxidative phosphorylationX syndromeCoenzyme Q deficiencyThermogenic respirationMitochondrial CoQTranscriptional silencingFMRP deficiencyFmr1 knockout miceQ deficiencyDysfunctional mitochondriaFMR1 geneFXS phenotypeOxidative phosphorylationMitochondrial respirationCommon genetic causeProtein synthesisFull mutationKey phenotypicPeak of synaptogenesisMitochondriaProtein expressionGenetic cause
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
2015
Decreased SGK1 Expression and Function Contributes to Behavioral Deficits Induced by Traumatic Stress
Licznerski P, Duric V, Banasr M, Alavian KN, Ota KT, Kang HJ, Jonas EA, Ursano R, Krystal JH, Duman RS, . Decreased SGK1 Expression and Function Contributes to Behavioral Deficits Induced by Traumatic Stress. PLOS Biology 2015, 13: e1002282. PMID: 26506154, PMCID: PMC4623974, DOI: 10.1371/journal.pbio.1002282.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsBehavior, AnimalCohort StudiesDendritic SpinesDepressive Disorder, MajorEnzyme RepressionFemaleGene Transfer TechniquesHippocampusHumansImmediate-Early ProteinsMaleMiddle AgedNerve Tissue ProteinsNeuronsPrefrontal CortexProtein Serine-Threonine KinasesRats, Sprague-DawleySignal TransductionStress Disorders, Post-TraumaticSynaptic TransmissionTissue BanksConceptsMajor depressive disorderPost-traumatic stress disorderPrefrontal cortexAbnormal dendritic spine morphologyCorticolimbic brain regionsAnhedonic-like behaviorInhibition of SGK1Dendritic spine morphologyKinase 1 expressionAmygdala of individualsTraumatic stressPostmortem prefrontal cortexSynaptic dysfunctionDepressive disorderBehavioral deficitsRodent modelsPTSD subjectsFunctional alterationsBrain regionsSGK1 expressionSpine morphologyStress disorderFunction contributesBehavioral changesDisorders
2014
Impaired import: how huntingtin harms
Jonas EA. Impaired import: how huntingtin harms. Nature Neuroscience 2014, 17: 747-749. PMID: 24866036, PMCID: PMC4448962, DOI: 10.1038/nn.3726.Peer-Reviewed Original Research
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
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
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 generationBAK 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