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 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
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 leakMaturationMetabolism
2019
Alpha-Tocotrienol Prevents Oxidative Stress-Mediated Post-Translational Cleavage of Bcl-xL in Primary Hippocampal Neurons
Park HA, Mnatsakanyan N, Broman K, Davis AU, May J, Licznerski P, Crowe-White KM, Lackey KH, Jonas EA. Alpha-Tocotrienol Prevents Oxidative Stress-Mediated Post-Translational Cleavage of Bcl-xL in Primary Hippocampal Neurons. International Journal Of Molecular Sciences 2019, 21: 220. PMID: 31905614, PMCID: PMC6982044, DOI: 10.3390/ijms21010220.Peer-Reviewed Original ResearchConceptsPrimary hippocampal neuronsHippocampal neuronsReactive oxygen speciesMitochondrial dysfunctionBcl-xLMitochondrial membrane potentialMitochondrial functionProduction of ROSExcitotoxic conditionsGlutamate challengeNeuroprotective propertiesMembrane potentialNeuronal deathExcitotoxic stimulationBcl-xL levelsNeuronal survivalIntracellular ATP depletionMitochondrial reactive oxygen speciesB cellsImportant causeDysfunctionNeuronsROS productionATP depletionNeurite outgrowthATP 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 ResearchMeSH KeywordsAdenosine TriphosphateBiological TransportCyclosporineHumansMitochondrial Membrane Transport ProteinsMitochondrial Permeability Transition PoreConceptsMitochondrial 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
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
2016
Physiological roles of the mitochondrial permeability transition pore
Mnatsakanyan N, Beutner G, Porter GA, Alavian KN, Jonas EA. Physiological roles of the mitochondrial permeability transition pore. Journal Of Bioenergetics And Biomembranes 2016, 49: 13-25. PMID: 26868013, PMCID: PMC4981558, DOI: 10.1007/s10863-016-9652-1.BooksConceptsMitochondrial permeability transition poreATP synthaseOxidative phosphorylationATP productionMulti-protein enzymeF1Fo-ATP synthaseMembrane potential maintenanceInner mitochondrial membraneSynaptic vesicle recyclingMembrane-inserted portionPermeability transition poreMitochondrial permeability transitionRegulatory complexC subunitCellular functionsVesicle recyclingMitochondrial membraneCardiac developmentRegulatory mechanismsMitochondrial productionTransition porePermeability transitionPhysiological roleCell deathEnzymatic portion
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.BooksConceptsMitochondrial 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
2011
The β Subunit Loop That Couples Catalysis and Rotation in ATP Synthase Has a Critical Length*
Mnatsakanyan N, Kemboi SK, Salas J, Weber J. The β Subunit Loop That Couples Catalysis and Rotation in ATP Synthase Has a Critical Length*. Journal Of Biological Chemistry 2011, 286: 29788-29796. PMID: 21705326, PMCID: PMC3191020, DOI: 10.1074/jbc.m111.254730.Peer-Reviewed Original Research
2009
ATP Synthase with Its γ Subunit Reduced to the N-terminal Helix Can Still Catalyze ATP Synthesis*
Mnatsakanyan N, Hook JA, Quisenberry L, Weber J. ATP Synthase with Its γ Subunit Reduced to the N-terminal Helix Can Still Catalyze ATP Synthesis*. Journal Of Biological Chemistry 2009, 284: 26519-26525. PMID: 19636076, PMCID: PMC2785340, DOI: 10.1074/jbc.m109.030528.Peer-Reviewed Original ResearchThe 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