2024
Molecular Profiling of Mouse Models of Loss or Gain of Function of the KCNT1 (Slack) Potassium Channel and Antisense Oligonucleotide Treatment
Sun F, Wang H, Wu J, Quraishi I, Zhang Y, Pedram M, Gao B, Jonas E, Nguyen V, Wu S, Mabrouk O, Jafar-nejad P, Kaczmarek L. Molecular Profiling of Mouse Models of Loss or Gain of Function of the KCNT1 (Slack) Potassium Channel and Antisense Oligonucleotide Treatment. Biomolecules 2024, 14: 1397. DOI: 10.3390/biom14111397.Peer-Reviewed Original ResearchWild-type miceKO miceSpectrum of epilepsy syndromesAntisense oligonucleotidesGain-of-function variantsAntisense oligonucleotide treatmentEpileptic phenotypePotassium channelsKCNT1Molecular profilingOligonucleotide treatmentAnimal modelsEpilepsy syndromesC-terminal mutationsIncreased expressionCerebral cortexMiceExpression of multiple proteinsComprehensive proteomic analysisDisease modelsCortical mitochondriaMolecular differencesDensity of mitochondrial cristaeMitochondrial membraneTreatmentSulfide 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 therapyProtonation-dependent ion flux in a mitochondrial leak channel
Wang Q, Mnatsakanyan N, Jonas E, Pias S. Protonation-dependent ion flux in a mitochondrial leak channel. Biophysical Journal 2024, 123: 522a. DOI: 10.1016/j.bpj.2023.11.3159.Peer-Reviewed Original Research
2023
Mitochondrial leak metabolism induces the Spemann-Mangold Organizer via Hif-1α in Xenopus
MacColl Garfinkel A, Mnatsakanyan N, Patel J, Wills A, Shteyman A, Smith P, Alavian K, Jonas E, Khokha M. Mitochondrial leak metabolism induces the Spemann-Mangold Organizer via Hif-1α in Xenopus. Developmental Cell 2023, 58: 2597-2613.e4. PMID: 37673063, PMCID: PMC10840693, DOI: 10.1016/j.devcel.2023.08.015.Peer-Reviewed Original ResearchConceptsSpemann-Mangold organizerATP productionMitochondrial respirationC subunit ringHIF-1αMitochondrial oxidative metabolismEmbryonic patterningCell fateATP synthaseC subunitVentral mesodermHIF-1α activationInstructive roleHypoxia-inducible factor-1αΒ-cateninGeneral mechanismXenopusFactor-1αRespirationMembrane leakOxidative metabolismMetabolismMesodermActivationOxygen consumptionIdentity, 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 permeabilityP27-029-23 Alpha-Tocotrienol: A Nutritional Regulator of Bcl-xL in Neurons
Park H, Crowe-White K, Ciesla L, Bannerman S, Scott M, Davis A, Adhikari B, Burnett G, Broman K, Ferdous K, Lackey K, Lickznerski P, Jonas E. P27-029-23 Alpha-Tocotrienol: A Nutritional Regulator of Bcl-xL in Neurons. Current Developments In Nutrition 2023, 7: 101236. DOI: 10.1016/j.cdnut.2023.101236.Peer-Reviewed Original Research
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 ResearchMitochondrial ATP synthase F1 subcomplex forms a gate of c-subunit leak channel
Mnatsakanyan N, Park H, Wu J, Jonas E. Mitochondrial ATP synthase F1 subcomplex forms a gate of c-subunit leak channel. Biochimica Et Biophysica Acta (BBA) - Bioenergetics 2022, 1863: 148774. DOI: 10.1016/j.bbabio.2022.148774.Peer-Reviewed Original ResearchThe Role of Alpha-Tocotrienol during Development of Primary Hippocampal Neurons
Park H, Crowe-White K, Ciesla L, Bannerman S, Scott M, Davis A, Adhikari B, Burnett G, Broman K, Ferdous K, Lackey K, Lickznerski P, Jonas E. The Role of Alpha-Tocotrienol during Development of Primary Hippocampal Neurons. Current Developments In Nutrition 2022, 6: 800. PMCID: PMC9194400, DOI: 10.1093/cdn/nzac064.019.Peer-Reviewed Original ResearchPrimary hippocampal neuronsHippocampal neuronsPrimary rat hippocampal neuronsRat hippocampal neuronsAlpha-tocotrienolProtein levelsBcl-xLMitochondrial functionMitochondrial superoxide levelsNeuroprotective propertiesNeuronal ATPSholl analysisNeurobasal mediumNeurite complexityB cellsVitamin ENeuron developmentNeuronsBeneficial effectsSuperoxide levelsNeuronal growthConditioned mediaNeurite morphologyIntracellular ATPMitochondrial superoxideMitochondrial 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 gradientAlpha-tocotrienol enhances arborization of primary hippocampal neurons via upregulation of Bcl-xL
Park HA, Crowe-White KM, Ciesla L, Scott M, Bannerman S, Davis AU, Adhikari B, Burnett G, Broman K, Ferdous KA, Lackey KH, Licznerski P, Jonas EA. Alpha-tocotrienol enhances arborization of primary hippocampal neurons via upregulation of Bcl-xL. Nutrition Research 2022, 101: 31-42. PMID: 35366596, PMCID: PMC9081260, DOI: 10.1016/j.nutres.2022.02.007.Peer-Reviewed Original ResearchConceptsPrimary hippocampal neuronsControl neuronsHippocampal neuronsAlpha-tocotrienolBcl-xLVitamin E familyCerebral ischemiaNeuronal viabilityMature neuronsB cellsNeurite complexityNeuronal functionMitochondrial energy productionBrain developmentCentral mechanismsNeuronsBeneficial effectsOxidative stressBcl-xL upregulationProtein levelsNeurite branchingTreatmentE familyATP levelsNeurite outgrowth
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 systemVitamin E Improves Neurite Complexity by Enhancing Mitochondrial Function
Park H, Crowe-White K, Davis A, Bannerman S, Burnett G, Scott M, Broman K, Lackey K, Licznerski P, Jonas E. Vitamin E Improves Neurite Complexity by Enhancing Mitochondrial Function. Current Developments In Nutrition 2021, 5: 5140915. PMCID: PMC8181647, DOI: 10.1093/cdn/nzab049_028.Peer-Reviewed Original ResearchPost-translational cleavagePrimary hippocampal neuronsBcl-xLMitochondrial functionHippocampal neuronsNeurite complexityNeurite outgrowthOxidative stressProtein levelsPotential therapeutic roleProtein Bcl-xLVitamin E familyATP/ADP ratioNormal physiological developmentNovel functionBrain injuryTherapeutic roleReal-time PCRSholl analysisNew synapsesNeurobasal mediumATP productionNeurite injuryControl groupVitamin EWetting Transitions in the ATP Synthase C-Subunit Ring, a Large-Conductance Ion Channel
Dotson R, Mnatsakanyan N, Jonas E, Pias S. Wetting Transitions in the ATP Synthase C-Subunit Ring, a Large-Conductance Ion Channel. Biophysical Journal 2021, 120: 194a. DOI: 10.1016/j.bpj.2020.11.1335.Peer-Reviewed Original ResearchPresynaptic Kv3 channels are required for fast and slow endocytosis of synaptic vesicles
Wu XS, Subramanian S, Zhang Y, Shi B, Xia J, Li T, Guo X, El-Hassar L, Szigeti-Buck K, Henao-Mejia J, Flavell RA, Horvath TL, Jonas EA, Kaczmarek LK, Wu LG. Presynaptic Kv3 channels are required for fast and slow endocytosis of synaptic vesicles. Neuron 2021, 109: 938-946.e5. PMID: 33508244, PMCID: PMC7979485, DOI: 10.1016/j.neuron.2021.01.006.Peer-Reviewed Original ResearchConceptsSlow endocytosisVesicle mobilizationF-actin cytoskeletonChannel mutationsPotassium channelsKv3.3 proteinsInhibits endocytosisRapid endocytosisNovel functionF-actinEndocytosisCrucial functionSynaptic vesiclesFamily channelsSynaptic transmissionDiscovery decadesMembrane potentialNeurotransmitter releaseDiverse neurological disordersIon conductanceMutationsReleasable poolMouse nerve terminalsPotassium channel mutationsPathological effectsMitochondria: powerhouses of presynaptic plasticity
Subramanian S, Jonas EA. Mitochondria: powerhouses of presynaptic plasticity. The Journal Of Physiology 2021, 599: 1363-1364. PMID: 33428213, PMCID: PMC7942974, DOI: 10.1113/jp281040.Peer-Reviewed Original Research
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 leakMaturationMetabolismOxidative stress battles neuronal Bcl-xL in a fight to the death
Park HA, Broman K, Jonas EA. Oxidative stress battles neuronal Bcl-xL in a fight to the death. Neural Regeneration Research 2020, 16: 12-15. PMID: 32788441, PMCID: PMC7818872, DOI: 10.4103/1673-5374.286946.Peer-Reviewed Original ResearchBcl-xLMitochondrial membraneBcl-xL.BCL2 proteinFO ATP synthaseBcl-XL bindsPost-translational phosphorylationOxidative stressBcl-x geneSynaptic vesicle recyclingActivation of caspasesPro-survival proteinsMitochondrial ATP productionAnti-apoptotic roleUndergoes proteolytic cleavageMultiprotein complexesATP synthaseTranscription factorsVesicle recyclingBCL2 familyApoptotic signalingKey regulatorPhysiological processesAlters formationATP productionThe 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 potentialRoles of Vitamin E in Energy Metabolism During Neurite Outgrowth
Stratton Z, Davis A, Jonas E, Crowe-White K, Park H. Roles of Vitamin E in Energy Metabolism During Neurite Outgrowth. Current Developments In Nutrition 2020, 4: nzaa057_051. PMCID: PMC7259054, DOI: 10.1093/cdn/nzaa057_051.Peer-Reviewed Original ResearchPrimary hippocampal neuronsBrain injuryHippocampal neuronsControl groupNeurite outgrowthNeuronal energy metabolismMaintenance of synapsesVitamin E familyEnergy metabolismNeurite lossNeurobasal mediumVitamin EAlpha-tocotrienolBrain developmentNeuronsOxidative stressNeurite growthBranched neuritesCentral targetMitochondrial inner membrane potentialE familyATP levelsTreatmentNeuritesInjury