2020
ATP Synthase c-Subunit Leak Causes Aberrant Cellular Metabolism in Fragile X Syndrome
Licznerski P, Park HA, Rolyan H, Chen R, Mnatsakanyan N, Miranda P, Graham M, Wu J, Cruz-Reyes N, Mehta N, Sohail S, Salcedo J, Song E, Effman C, Effman S, Brandao L, Xu GN, Braker A, Gribkoff VK, Levy RJ, Jonas EA. ATP Synthase c-Subunit Leak Causes Aberrant Cellular Metabolism in Fragile X Syndrome. Cell 2020, 182: 1170-1185.e9. PMID: 32795412, PMCID: PMC7484101, DOI: 10.1016/j.cell.2020.07.008.Peer-Reviewed Original ResearchConceptsFragile X syndromeC subunitAberrant synaptic developmentHuman fragile X syndromeATP synthase enzymeMental retardation proteinX syndromeATP production efficiencyMRNA translation rateAberrant cellular metabolismATP synthaseMRNA translationTranslation rateCellular metabolismSynaptic growthSynthase enzymeMouse neuronsSynapse maturationSynaptic developmentPharmacological inhibitionLeak channelsSynaptic maturationMembrane leakMaturationMetabolismATP synthase c-subunit ring as the channel of mitochondrial permeability transition: Regulator of metabolism in development and degeneration
Mnatsakanyan N, Jonas EA. ATP synthase c-subunit ring as the channel of mitochondrial permeability transition: Regulator of metabolism in development and degeneration. Journal Of Molecular And Cellular Cardiology 2020, 144: 109-118. PMID: 32461058, PMCID: PMC7877492, DOI: 10.1016/j.yjmcc.2020.05.013.Peer-Reviewed Original ResearchConceptsMitochondrial permeability transition poreC subunit ringMitochondrial permeability transitionPermeability transitionRegulator of metabolismPermeability transition poreImportant metabolic regulatorMitochondrial megachannelBiology todayRegulatory mechanismsCentral playerTransition poreMetabolic regulatorMolecular compositionRecent findingsRegulatorDegenerative diseasesPathophysiological roleRecent advancesMegachannelRoleMetabolismMysterious phenomenon
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 toxicity
2014
An uncoupling channel within the c-subunit ring of the F1FO ATP synthase is the mitochondrial permeability transition pore
Alavian KN, Beutner G, Lazrove E, Sacchetti S, Park HA, Licznerski P, Li H, Nabili P, Hockensmith K, Graham M, Porter GA, Jonas EA. An uncoupling channel within the c-subunit ring of the F1FO ATP synthase is the mitochondrial permeability transition pore. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 10580-10585. PMID: 24979777, PMCID: PMC4115574, DOI: 10.1073/pnas.1401591111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCell DeathHEK293 CellsHumansIon Channel GatingIon ChannelsLiposomesMitochondriaMitochondrial Membrane Transport ProteinsMitochondrial MembranesMitochondrial Permeability Transition PoreMutationProtein ConformationProtein SubunitsProton-Translocating ATPasesRatsReactive Oxygen SpeciesConceptsMitochondrial PT poreF1Fo-ATP synthaseATP synthasePermeability transitionCell deathCellular metabolic efficiencyInner mitochondrial membrane permeabilityOxygen species-induced cell deathC subunit ringATP synthase F1Mitochondrial membrane permeabilityMitochondrial permeability transitionC subunitPT poreTight regulationATP productionMolecular identitySingle-channel conductanceChannel closureLeak channelsMPTP openingMetabolic efficiencyMembrane permeabilityHealthy cellsOsmotic shifts
2008
PKC-Induced Intracellular Trafficking of CaV2 Precedes Its Rapid Recruitment to the Plasma Membrane
Zhang Y, Helm JS, Senatore A, Spafford JD, Kaczmarek LK, Jonas EA. PKC-Induced Intracellular Trafficking of CaV2 Precedes Its Rapid Recruitment to the Plasma Membrane. Journal Of Neuroscience 2008, 28: 2601-2612. PMID: 18322103, PMCID: PMC2830008, DOI: 10.1523/jneurosci.4314-07.Peer-Reviewed Original ResearchConceptsProtein kinase CActivation of PKCPlasma membraneGrowth conesLatrunculin BIntracellular traffickingActin polymerizationIntact microtubulesIntact actinKinase CChannel insertionPKC activationIon channelsMicrotubule polymerizationRapid recruitmentOrganellesLamellipodiumSubunitsMicrotubulesActinMembraneActivationRecruitmentCone terminalsNew sites