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
2022
Mitochondrial 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 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
ATP 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
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
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