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
2020
The new role of F1Fo ATP synthase in mitochondria-mediated neurodegeneration and neuroprotection
Mnatsakanyan N, Jonas EA. The new role of F1Fo ATP synthase in mitochondria-mediated neurodegeneration and neuroprotection. Experimental Neurology 2020, 332: 113400. PMID: 32653453, PMCID: PMC7877222, DOI: 10.1016/j.expneurol.2020.113400.Peer-Reviewed Original ResearchConceptsMitochondrial inner membraneATP synthaseInner membraneOxidative phosphorylationF1Fo-ATP synthaseUnique rotational mechanismMitochondrial inner membrane potentialEfficient cellular metabolismInner membrane potentialMitochondrial permeability transition porePermeability transition poreUnique regulatorAbundant proteinsNew roleCellular metabolismCell lifeProton translocationATP synthesisTransition poreCell survivalElectrochemical gradientCertain pathophysiological conditionsSynthaseATPMembrane potential
2019
A mitochondrial megachannel resides in monomeric F1FO ATP synthase
Mnatsakanyan N, Llaguno MC, Yang Y, Yan Y, Weber J, Sigworth FJ, Jonas EA. A mitochondrial megachannel resides in monomeric F1FO ATP synthase. Nature Communications 2019, 10: 5823. PMID: 31862883, PMCID: PMC6925261, DOI: 10.1038/s41467-019-13766-2.Peer-Reviewed Original ResearchConceptsATP synthase monomersMitochondrial permeability transition poreATP synthaseGiant unilamellar vesiclesMitochondrial megachannelOligomeric stateSmall unilamellar vesiclesF1Fo-ATP synthaseMitochondrial ATP synthaseMitochondrial inner membraneCryo-EM density mapsPermeability transition porePorcine heart mitochondriaUnilamellar vesiclesInner membraneMPTP activityTransition poreElectron cryomicroscopyChannel activityLipid compositionDimer formationHeart mitochondriaSynthaseChannel formationVesicles
2017
Inhibition of Bcl-xL prevents pro-death actions of ΔN-Bcl-xL at the mitochondrial inner membrane during glutamate excitotoxicity
Park HA, Licznerski P, Mnatsakanyan N, Niu Y, Sacchetti S, Wu J, Polster BM, Alavian KN, Jonas EA. Inhibition of Bcl-xL prevents pro-death actions of ΔN-Bcl-xL at the mitochondrial inner membrane during glutamate excitotoxicity. Cell Death & Differentiation 2017, 24: 1963-1974. PMID: 28777375, PMCID: PMC5635221, DOI: 10.1038/cdd.2017.123.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsBcl-X ProteinBiphenyl CompoundsCell DeathCyclosporineGlutamic AcidMembrane Potential, MitochondrialMitochondrial MembranesMitochondrial Proton-Translocating ATPasesModels, BiologicalMutant ProteinsNeuritesNeurotoxinsNitrophenolsPiperazinesProtein SubunitsRats, Sprague-DawleyRhodaminesSulfonamidesConceptsBcl-xLABT-737ΔN-BclMitochondrial membraneWEHI-539ATP synthase c-subunitMitochondrial inner membrane depolarizationPro-death actionInner membrane depolarizationMitochondrial inner membraneOuter mitochondrial membraneMitochondrial inner membrane potentialATP synthase activityActivation of BaxInner membrane potentialMitochondrial permeability transition poreMitochondrial membrane potentialMembrane potentialPermeability transition poreAnti-apoptotic activityC subunitInner membraneB-cell lymphoma extra-large proteinBax activationGlutamate toxicityThe Mitochondrial Permeability Transition Pore: Molecular Structure and Function in Health and Disease
Jonas E, Porter G, Beutner G, Mnatsakanyan N, Park H, Mehta N, Chen R, Alavian K. The Mitochondrial Permeability Transition Pore: Molecular Structure and Function in Health and Disease. Biological And Medical Physics, Biomedical Engineering 2017, 69-105. DOI: 10.1007/978-3-319-55539-3_3.Peer-Reviewed Original ResearchMitochondrial permeability transition porePermeability transition poreCell deathTransition poreMitochondrial inner membraneInner mitochondrial membraneC subunitATP synthaseInner membraneOuter membraneMitochondrial membraneCardiac developmentRegulatory mechanismsOxidative phosphorylationATP productionMitochondrial functionMolecular componentsMitochondrial efficiencyOsmotic dysregulationCell functionLarge conductanceRecent findingsPersistent openingMembraneIon transportExamination of Mitochondrial Ion Conductance by Patch Clamp in Intact Neurons and Mitochondrial Membrane Preparations
Jonas E, Mnatsakanyan N. Examination of Mitochondrial Ion Conductance by Patch Clamp in Intact Neurons and Mitochondrial Membrane Preparations. Neuromethods 2017, 123: 211-238. DOI: 10.1007/978-1-4939-6890-9_11.Peer-Reviewed Original ResearchMitochondrial calcium uniporterMitochondrial permeability transition poreInner membraneCell deathOuter membraneIon channelsBcl-2 family proteinsNumerous cellular processesMitochondrial ion channelsComplex of proteinsChannel activityTrafficking of metabolitesPro-death stimuliMitochondrial membrane preparationsPermeability transition poreIon channel activityMembrane compartmentalizationIon channel complexDeath channelATP synthaseCellular processesFamily proteinsCalcium uniporterMolecular participantsATP production
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
2013
F1FO 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
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 transmissionVDACMitochondrial 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
Unique Mitochondrial Ion Channels: Roles in Synaptic Transmission and Programmed Cell Death
Jonas E. Unique Mitochondrial Ion Channels: Roles in Synaptic Transmission and Programmed Cell Death. 2008, 155-191. DOI: 10.1002/9780470429907.ch6.Peer-Reviewed Original Research
2004
Ion channels on intracellular organelles
Kaczmarek L, Jonas E. Ion channels on intracellular organelles. Advances In Molecular And Cell Biology 2004, 32: 433-458. DOI: 10.1016/s1569-2558(03)32018-1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsExternal signalsIon channelsCellular functionsInner membraneMitochondrial channelsIntracellular membranesPlasma membraneIntracellular organellesMolecular identityCell deathCytoplasmic calcium levelsHandling of calciumRyanodine receptorProperties of channelsCytoplasmic calciumIntracellular storesPotential roleRelease of calciumInternal storesMembraneRegulationKey roleSynaptic transmissionCalcium influxIntracellular calcium