2022
Fluid shear stress enhances proliferation of breast cancer cells via downregulation of the c-subunit of the F1FO ATP synthase
Park HA, Brown SR, Jansen J, Dunn T, Scott M, Mnatsakanyan N, Jonas EA, Kim Y. Fluid shear stress enhances proliferation of breast cancer cells via downregulation of the c-subunit of the F1FO ATP synthase. Biochemical And Biophysical Research Communications 2022, 632: 173-180. PMID: 36209586, PMCID: PMC10024463, DOI: 10.1016/j.bbrc.2022.09.084.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateBreast NeoplasmsCell ProliferationDown-RegulationFemaleHumansMitochondrial Proton-Translocating ATPasesOxygenMitochondrial 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 ResearchMeSH KeywordsAdenosine TriphosphateCell DeathHumansMitochondrial Membrane Transport ProteinsMitochondrial Permeability Transition PoreMitochondrial Proton-Translocating ATPasesProton-Translocating ATPasesConceptsMitochondrial 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
ATP 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 ResearchMeSH KeywordsAnimalsDisease SusceptibilityEnergy MetabolismHumansMitochondriaMitochondrial MembranesMitochondrial Proton-Translocating ATPasesModels, MolecularNeuronal PlasticityNeuronsPermeabilityProtein ConformationProtein SubunitsConceptsMitochondrial 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 ResearchMeSH KeywordsAnimalsCalciumCryoelectron MicroscopyMitochondria, HeartMitochondrial MembranesMitochondrial Proton-Translocating ATPasesProtein SubunitsSwineUnilamellar LiposomesConceptsATP 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 formationVesiclesParkinson’s disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth
Chen R, Park HA, Mnatsakanyan N, Niu Y, Licznerski P, Wu J, Miranda P, Graham M, Tang J, Boon AJW, Cossu G, Mandemakers W, Bonifati V, Smith PJS, Alavian KN, Jonas EA. Parkinson’s disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth. Cell Death & Disease 2019, 10: 469. PMID: 31197129, PMCID: PMC6565618, DOI: 10.1038/s41419-019-1679-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDopaminergic NeuronsGene ExpressionHumansMembrane Potential, MitochondrialMiceMice, Inbred C57BLMice, KnockoutMitochondriaMitochondrial MembranesMitochondrial Proton-Translocating ATPasesProtein BindingProtein Deglycase DJ-1Rats, Sprague-DawleyConceptsDJ-1C subunitATP synthaseParkinson's disease protein DJ-1Β-subunitProtein componentsATP synthase β subunitMitochondrial uncouplingDJ-1 bindsATP synthase efficiencyATP synthase F1Synthase β subunitATP production efficiencyProtein DJ-1Neuronal process extensionProtein levelsNeuronal process outgrowthDJ-1 knockoutWild-type counterpartsSubunit protein levelsDJ-1 mutationsSevere defectsCell metabolismKO neuronsKO cultures
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
2015
Cell death disguised: The mitochondrial permeability transition pore as the c-subunit of the F1FO ATP synthase
Jonas EA, Porter GA, Beutner G, Mnatsakanyan N, Alavian KN. Cell death disguised: The mitochondrial permeability transition pore as the c-subunit of the F1FO ATP synthase. Pharmacological Research 2015, 99: 382-392. PMID: 25956324, PMCID: PMC4567435, DOI: 10.1016/j.phrs.2015.04.013.BooksMeSH KeywordsAdenosine TriphosphateAnimalsCell DeathMitochondriaMitochondrial Membrane Transport ProteinsMitochondrial MembranesMitochondrial Permeability Transition PoreMitochondrial Proton-Translocating ATPasesConceptsMitochondrial permeability transition poreATP synthaseC subunitCell deathF1Fo-ATP synthaseInner mitochondrial membranePermeability transition poreMitochondrial permeability transitionOuter membraneMitochondrial membraneRegulatory mechanismsOxidative phosphorylationATP productionTransition poreMitochondrial functionPermeability transitionMolecular componentsOsmotic dysregulationLarge conductancePathological roleRecent findingsPersistent openingSynthaseIon transportMembrane
2009
The Role of the βDELSEED-loop of ATP Synthase*
Mnatsakanyan N, Krishnakumar AM, Suzuki T, Weber J. The Role of the βDELSEED-loop of ATP Synthase*. Journal Of Biological Chemistry 2009, 284: 11336-11345. PMID: 19246448, PMCID: PMC2670139, DOI: 10.1074/jbc.m900374200.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAmino Acid SequenceATP Synthetase ComplexesBacillusBinding SitesCell MembraneEscherichia coliMitochondrial Proton-Translocating ATPasesMolecular ConformationMolecular Sequence DataMutationNucleotidesPhosphorylationProtein Structure, TertiarySequence Homology, Amino AcidConceptsWild-type enzymeATP synthaseDELSEED-loopDeletion mutantsATP hydrolysisUnique rotational mechanismTransmembrane proton gradientHelix motifRate-limiting catalytic stepTerminal domainFunctional analysisMutantsBeta subunitMembrane vesiclesATP synthesisProton gradientAmino acidsLow abundanceCatalytic stepMechanochemical couplingCatalytic siteSynthaseChemical energyEnzymeMembrane preparations