2024
Sulfide quinone oxidoreductase contributes to voltage sensing of the mitochondrial permeability transition pore
Griffiths K, Wang A, Jonas E, Levy R. Sulfide quinone oxidoreductase contributes to voltage sensing of the mitochondrial permeability transition pore. The FASEB Journal 2024, 38: e23494. PMID: 38376922, PMCID: PMC11082757, DOI: 10.1096/fj.202301280r.Peer-Reviewed Original ResearchConceptsMitochondrial permeability transition poreSulfide quinone oxidoreductasePermeability transition poreTransition poreFragile X syndromeQuinone oxidoreductaseMouse heart mitochondriaHeart mitochondriaGenetic silencingAlzheimer's diseaseCardiac mitochondriaPharmacological inhibitionMitochondriaOpen probabilityOxidoreductaseX syndromeTherapeutic targetIncreased expressionModel systemLack of translationVoltage-gated channelsIsolated-perfused heartsPathological openingMyocardial ischemiaClinical therapy
2023
Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions
Bernardi P, Gerle C, Halestrap A, Jonas E, Karch J, Mnatsakanyan N, Pavlov E, Sheu S, Soukas A. Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions. Cell Death & Differentiation 2023, 30: 1869-1885. PMID: 37460667, PMCID: PMC10406888, DOI: 10.1038/s41418-023-01187-0.Peer-Reviewed Original ResearchConceptsMitochondrial permeability transition poreMitochondrial permeability transitionAdenine nucleotide translocasePermeability transition poreATP synthase dimersTransition poreInner mitochondrial membrane permeabilityC subunit ringOuter mitochondrial membraneMitochondrial membrane permeabilityDeath of cellsMPTP openingNecrotic cell deathMitochondrial membraneNucleotide translocaseTransient mPTP openingMitochondrial bioenergeticsSub-conductance statesMolecular identityPermeability transitionCell deathPhysiological roleNon-selective channelsDiscovery decadesMembrane permeability
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 potentialATP 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 phenomenonStructural 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 formationVesiclesATP 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 ResearchConceptsMitochondrial 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
The 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 transportNew Insights into the Molecular Structure and Regulation of the Mitochondrial Permeability Transition Pore
Mnatsakanyan N, Park H, Wu J, Miranda P, Jonas E. New Insights into the Molecular Structure and Regulation of the Mitochondrial Permeability Transition Pore. Biophysical Journal 2017, 112: 440a. DOI: 10.1016/j.bpj.2016.11.2349.Peer-Reviewed Original Research
2016
The Mitochondrial Permeability Transition Pore and ATP Synthase
Beutner G, Alavian K, Jonas EA, Porter GA. The Mitochondrial Permeability Transition Pore and ATP Synthase. Handbook Of Experimental Pharmacology 2016, 240: 21-46. PMID: 27590224, PMCID: PMC7439278, DOI: 10.1007/164_2016_5.BooksConceptsPermeability transition poreElectron transport chainATP synthaseGeneration of ATPMitochondrial permeability transition poreATP generationTransition poreCell deathC subunit ringMitochondrial ATP generationFo subunitsEmbryonic mouse heartPTP openingTransport chainOxidative phosphorylationEquivalents NADHMature cellsSynthasePhysiologic roleMouse heartsATPRecent studiesPhosphorylationSubunitsFADH2Physiological 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 transportMembraneABT‐737 Inhibits Full Length And Cleaved Pro‐Apoptotic Bcl‐xL, Resulting in Differential Effects on Death And Survival
Park H, Licznerski P, Niu Y, Alavian K, Jonas E. ABT‐737 Inhibits Full Length And Cleaved Pro‐Apoptotic Bcl‐xL, Resulting in Differential Effects on Death And Survival. The FASEB Journal 2015, 29 DOI: 10.1096/fasebj.29.1_supplement.777.4.Peer-Reviewed Original ResearchFull-length Bcl-xLBcl-xLABT-737Mitochondrial potentialATP productionΔN-BclAnti-apoptotic Bcl-2 family proteinsBcl-2 family proteinsCell death stimuliMitochondrial membrane permeabilityATP synthase activityMitochondrial permeability transition porePro-apoptotic BclPro-apoptotic formBcl-xL inhibitorsPermeability transition poreDeath stimuliFamily proteinsBcl-xL.Isolated mitochondriaPharmacological inhibitorsTransition poreCell deathFull lengthSynthase activity
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 production
2005
The Role of the Mitochondrial Apoptosis Induced Channel MAC in Cytochrome c Release
Martinez-Caballero S, Dejean LM, Jonas EA, Kinnally KW. The Role of the Mitochondrial Apoptosis Induced Channel MAC in Cytochrome c Release. Journal Of Bioenergetics And Biomembranes 2005, 37: 155-164. PMID: 16167172, DOI: 10.1007/s10863-005-6570-z.Peer-Reviewed Original ResearchConceptsMitochondrial apoptosis-induced channelBcl-2 family proteinsMitochondrial outer membraneCytochrome cOuter membrane integrityCytochrome c releaseHigh-conductance channelPermeability transition poreIntermembrane spaceFamily proteinsCommitment stepOuter membraneC releaseProapoptotic factorsTransition poreSingle-channel behaviorMAC formationMembrane integrityCrucial eventEarly apoptosisApoptosisMolecular compositionRelease channelMAC activityMitochondria