2021
Alteration of the F1Fo ATP Synthase Causes Metabolic Remodeling in Breast Cancer Cells
Dunn T, Mnatsakanyan N, Brown S, Jansen J, Hayden M, Jonas E, Kim Y, Park H. Alteration of the F1Fo ATP Synthase Causes Metabolic Remodeling in Breast Cancer Cells. Current Developments In Nutrition 2021, 5: 266. PMCID: PMC8182114, DOI: 10.1093/cdn/nzab036_008.Peer-Reviewed Original ResearchATP synthase subunitsF1Fo-ATP synthaseSynthase subunitsATP synthaseFluid shear stressBreast cancer cellsMDA-MB-231 human breast cancer cellsEnergy metabolismCancer cellsMetabolic remodelingHuman breast cancer cellsOxygen consumption rateIntracellular ATPMitochondrial energy metabolismMDA-MB-231 breast cancer cellsMetastatic cancer cellsC subunitCell divisionMitochondrial remodelingMultienzyme complexMDA-MB-231 cellsReactive oxygen speciesIntracellular energy metabolismATP productionActive transport system
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 potentialStructural and Pharmacological Characterization of the Mitochondrial Permeability Transition Pore: A Megachannel Formed by F1FO ATP Synthase
Mnatsakanyan N, Llaguno M, Yang Y, Yan Y, Weber J, Sigworth F, Jonas E. Structural and Pharmacological Characterization of the Mitochondrial Permeability Transition Pore: A Megachannel Formed by F1FO ATP Synthase. Biophysical Journal 2020, 118: 1a. DOI: 10.1016/j.bpj.2019.11.198.Peer-Reviewed Original Research
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
Phylogenetic Profiling of Mitochondrial Proteins and Integration Analysis of Bacterial Transcription Units Suggest Evolution of F1Fo ATP Synthase from Multiple Modules
Niu Y, Moghimyfiroozabad S, Safaie S, Yang Y, Jonas EA, Alavian KN. Phylogenetic Profiling of Mitochondrial Proteins and Integration Analysis of Bacterial Transcription Units Suggest Evolution of F1Fo ATP Synthase from Multiple Modules. Journal Of Molecular Evolution 2017, 85: 219-233. PMID: 29177973, PMCID: PMC5709465, DOI: 10.1007/s00239-017-9819-3.Peer-Reviewed Original ResearchConceptsBacterial transcription unitsF1Fo-ATP synthaseHuman mitochondrial proteinsTranscription unitATP synthaseMitochondrial proteinsPhylogenetic profilesF-type ATP synthaseATP synthase genesSeparate transcription unitsKingdoms of lifeATP synthase complexPeripheral stalk subunitsC subunit ringComplex evolutionary processesAncestral modulesPhylogenetic profilingModular evolutionSynthase complexBacterial genomesUniversal enzymeSynthase geneBacterial classesIndependent assemblyΑ3β3 hexamer
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
The Mitochondrial Permeability Transition Pore, the c‐Subunit of the F1Fo ATP Synthase, Cellular Development, and Synaptic Efficiency
Jonas E, Porter G, Beutner G, Mnatsakanyan N, Alavian K. The Mitochondrial Permeability Transition Pore, the c‐Subunit of the F1Fo ATP Synthase, Cellular Development, and Synaptic Efficiency. 2015, 31-64. DOI: 10.1002/9781119017127.ch2.Peer-Reviewed Original ResearchMitochondrial permeability transition poreMitochondrial membrane permeabilizationPermeability transition poreATP synthaseC subunitCell deathOuter mitochondrial membrane permeabilizationTransition poreF1Fo-ATP synthaseInner mitochondrial membraneMembrane channel activityMitochondrial permeability transitionMetabolic plasticityPT poreOuter membraneCellular developmentMembrane permeabilizationMitochondrial membraneRegulatory mechanismsOxidative phosphorylationAdenosine triphosphate (ATP) productionMitochondrial functionPermeability transitionMolecular componentsTriphosphate productionCell 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
2014
The Mitochondrial Complex V–Associated Large-Conductance Inner Membrane Current Is Regulated by Cyclosporine and Dexpramipexole
Alavian KN, Dworetzky SI, Bonanni L, Zhang P, Sacchetti S, Li H, Signore AP, Smith PJ, Gribkoff VK, Jonas EA. The Mitochondrial Complex V–Associated Large-Conductance Inner Membrane Current Is Regulated by Cyclosporine and Dexpramipexole. Molecular Pharmacology 2014, 87: 1-8. PMID: 25332381, PMCID: PMC4279080, DOI: 10.1124/mol.114.095661.Peer-Reviewed Original ResearchConceptsF1Fo-ATP synthaseInner mitochondrial membraneATP synthaseMitochondrial permeability transition poreSubmitochondrial vesiclesOligomycin sensitivity-conferring protein subunitMitochondrial membraneMitochondrial F1Fo-ATP synthaseMitochondrial matrix calciumFunctional conformational changesCellular energy productionHydrolysis of ATPPermeability transition poreC subunitIon conductanceATP/ADPProtein subunitsEnzyme complexOxidative phosphorylationConformational changesTransition poreComplex VLeak conductanceMatrix calciumEnergy productionAn 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
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
2012
The C-Subunit Ring of the F1FO ATP Synthase Constitutes a Leak Channel that Regulates Cellular Metabolic Efficiency by Counteracting the H+ Translocator
Alavian K, Lazrove E, Nabili P, Li H, Jonas E. The C-Subunit Ring of the F1FO ATP Synthase Constitutes a Leak Channel that Regulates Cellular Metabolic Efficiency by Counteracting the H+ Translocator. Biophysical Journal 2012, 102: 571a. DOI: 10.1016/j.bpj.2011.11.3110.Peer-Reviewed Original Research
2011
Erratum: Bcl-xL regulates metabolic efficiency of neurons through interaction with the mitochondrial F1FO ATP synthase
Alavian K, Li H, Collis L, Bonanni L, Zeng L, Sacchetti S, Lazrove E, Nabili P, Flaherty B, Graham M, Chen Y, Messerli S, Mariggio M, Rahner C, McNay E, Shore G, Smith P, Hardwick J, Jonas E. Erratum: Bcl-xL regulates metabolic efficiency of neurons through interaction with the mitochondrial F1FO ATP synthase. Nature Cell Biology 2011, 13: 1383-1383. DOI: 10.1038/ncb2369.Peer-Reviewed Original ResearchMitochondrial F1Fo-ATP synthaseF1Fo-ATP synthaseBcl-xL regulates metabolic efficiency of neurons through interaction with the mitochondrial F1FO ATP synthase
Alavian KN, Li H, Collis L, Bonanni L, Zeng L, Sacchetti S, Lazrove E, Nabili P, Flaherty B, Graham M, Chen Y, Messerli SM, Mariggio MA, Rahner C, McNay E, Shore GC, Smith PJ, Hardwick JM, Jonas EA. Bcl-xL regulates metabolic efficiency of neurons through interaction with the mitochondrial F1FO ATP synthase. Nature Cell Biology 2011, 13: 1224-1233. PMID: 21926988, PMCID: PMC3186867, DOI: 10.1038/ncb2330.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsBcl-2 Homologous Antagonist-Killer ProteinBcl-2-Associated X ProteinBcl-X ProteinBiphenyl CompoundsCarbonyl Cyanide p-TrifluoromethoxyphenylhydrazoneCells, CulturedEnergy MetabolismEnzyme InhibitorsHippocampusHydrolysisMembrane Potential, MitochondrialMitochondriaMitochondrial MembranesMitochondrial Proton-Translocating ATPasesNeuronsNitrophenolsOligomycinsOxygen ConsumptionPatch-Clamp TechniquesPiperazinesProton IonophoresRatsRecombinant Fusion ProteinsRNA InterferenceSulfonamidesSynapsesTime FactorsTransfectionConceptsBcl-xLSynthase complexATP synthaseMitochondrial F1Fo-ATP synthaseAnti-apoptotic BCL2 family proteinsF1Fo-ATP synthaseATP synthase complexF1FO-ATPase activityBcl-xL activityATPase activityBcl-xL proteinBCL2 family proteinsEndogenous Bcl-xLPresence of ATPFamily proteinsATPase complexNormal neuronal functionMembrane leak conductanceSubmitochondrial vesiclesΒ-subunitProtect cellsGenetic inhibitionMitochondrial efficiencyF1FoApoptotic molecules