2024
Sulfide quinone oxidoreductase contributes to voltage sensing of the mitochondrial permeability transition pore
Griffiths K, Wang A, Jonas E, Levy R. Sulfide quinone oxidoreductase contributes to voltage sensing of the mitochondrial permeability transition pore. The FASEB Journal 2024, 38: e23494. PMID: 38376922, PMCID: PMC11082757, DOI: 10.1096/fj.202301280r.Peer-Reviewed Original ResearchConceptsMitochondrial permeability transition poreSulfide quinone oxidoreductasePermeability transition poreTransition poreFragile X syndromeQuinone oxidoreductaseMouse heart mitochondriaHeart mitochondriaGenetic silencingAlzheimer's diseaseCardiac mitochondriaPharmacological inhibitionMitochondriaOpen probabilityOxidoreductaseX syndromeTherapeutic targetIncreased expressionModel systemLack of translationVoltage-gated channelsIsolated-perfused heartsPathological openingMyocardial ischemiaClinical therapy
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
2019
ATP Synthase C-Subunit-Deficient Mitochondria Have a Small Cyclosporine A-Sensitive Channel, but Lack the Permeability Transition Pore
Neginskaya MA, Solesio ME, Berezhnaya EV, Amodeo GF, Mnatsakanyan N, Jonas EA, Pavlov EV. ATP Synthase C-Subunit-Deficient Mitochondria Have a Small Cyclosporine A-Sensitive Channel, but Lack the Permeability Transition Pore. Cell Reports 2019, 26: 11-17.e2. PMID: 30605668, PMCID: PMC6521848, DOI: 10.1016/j.celrep.2018.12.033.Peer-Reviewed Original ResearchConceptsMitochondrial PT poreC subunitPermeability transitionMitochondrial inner membrane permeabilityPermeability transition poreInner membrane permeabilityATP synthasePT poreBongkrekic acidLarge conductance channelTransition poreMitochondrial functionCell deathParental cellsMitochondriaChannel activityMembrane permeabilityLow-conductance channelsConductance channelLow conductanceSensitive channelsSynthaseConductanceCellsDisruption
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
2009
Mitochondrial Ion Channels in Ischemic Brain
Jonas E. Mitochondrial Ion Channels in Ischemic Brain. Contemporary Clinical Neuroscience 2009, 117-150. DOI: 10.1007/978-1-60327-579-8_7.Peer-Reviewed Original ResearchIon channel activityBcl-2 family proteinsCell deathMitochondrial intermembrane spaceCytochrome cMitochondrial ion channelsChannel activityEnergy-dependent eventsIntermembrane spaceIon channel componentsCellular processesFamily proteinsInner membraneOuter membraneOxidative phosphorylationCell lifeProapoptotic factorsProapoptotic moleculesMitochondriaIon channelsCytosolic levelsCurrent knowledgeNormal brain functionDependent eventsEnergy deprivation
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
2007
Hypoxia increases BK channel activity in the inner mitochondrial membrane
Gu XQ, Siemen D, Parvez S, Cheng Y, Xue J, Zhou D, Sun X, Jonas EA, Haddad GG. Hypoxia increases BK channel activity in the inner mitochondrial membrane. Biochemical And Biophysical Research Communications 2007, 358: 311-316. PMID: 17481584, DOI: 10.1016/j.bbrc.2007.04.110.Peer-Reviewed Original Research
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
The 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
Proapoptotic 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 neuronsRegulation of Synaptic Transmission by Mitochondrial Ion Channels
Jonas E. Regulation of Synaptic Transmission by Mitochondrial Ion Channels. Journal Of Bioenergetics And Biomembranes 2004, 36: 357-361. PMID: 15377872, DOI: 10.1023/b:jobb.0000041768.11006.90.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBcl-X ProteinCell HypoxiaCell MembraneDecapodiformesElectric ConductivityHomeostasisHumansIon Channel GatingIon ChannelsMembrane PotentialsMitochondriaMitochondrial ProteinsNeuronsOxidative StressPorinsProto-Oncogene Proteins c-bcl-2Synaptic TransmissionVoltage-Dependent Anion ChannelsConceptsMitochondrial outer membraneVoltage-dependent anion channelOuter membraneBcl-xLSynaptic transmissionChannel activityNeuronal presynaptic terminalsMitochondrial ion channelsProteolytic fragmentsBcl-xL proteinRelease of ATPIon channel activityPresynaptic terminalsRapid onsetSynaptic functionNeurotransmitter releaseBcl-xL.Anion channelNeurotransmitter secretionPrevents cleavageHypoxiaIon channelsProtease inhibitorsLarge conductanceMitochondria
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
1999
Prolonged Activation of Mitochondrial Conductances During Synaptic Transmission
Jonas E, Buchanan J, Kaczmarek L. Prolonged Activation of Mitochondrial Conductances During Synaptic Transmission. Science 1999, 286: 1347-1350. PMID: 10558987, DOI: 10.1126/science.286.5443.1347.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsCalciumCalcium ChannelsDecapodiformesElectric ConductivityElectric StimulationIntracellular MembranesIon ChannelsIon TransportMicroscopy, ElectronMitochondriaPatch-Clamp TechniquesPorinsPresynaptic TerminalsSynaptic TransmissionTime FactorsVoltage-Dependent Anion ChannelsConceptsChannel activityIon channel activityMitochondrial membraneOnly organellesIntracellular organellesIntact cellsIon channelsMitochondriaOrganellesLarge conductanceTens of secondsPresynaptic terminalsIon transportSynaptic transmissionSynaptic stimulationConductanceElectron microscopyPatch-clamp techniqueMembraneActivityCellsActivationSquidStimulation