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 consumption
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 E
2020
Oxidative 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 productionCellular Mechanisms of Metabolic Remodeling During Fluid Sheer Stress-Induced Metastasis
Dunn T, Brown S, Mnatsakanyan N, Jonas E, Yonghyun K, Park H. Cellular Mechanisms of Metabolic Remodeling During Fluid Sheer Stress-Induced Metastasis. Current Developments In Nutrition 2020, 4: nzaa044_021. PMCID: PMC7258028, DOI: 10.1093/cdn/nzaa044_021.Peer-Reviewed Original ResearchATP synthaseC subunitBreast cancer cellsMDA-MB-231 cellsMetabolic remodelingCancer cellsCellular mechanismsEnergy metabolismKey enzyme complexMitochondrial energy metabolismMDA-MB-231 breast cancer cellsMDA-MB-231 human breast cancer cellsCell divisionMitochondrial remodelingEnzyme complexHuman breast cancer cellsATP productionMetastatic phenotypeActive transport systemUncoupler FCCPMitochondrial ATPProtein levelsIntracellular ATPATPAbundance
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 transportExamination of Mitochondrial Ion Conductance by Patch Clamp in Intact Neurons and Mitochondrial Membrane Preparations
Jonas E, Mnatsakanyan N. Examination of Mitochondrial Ion Conductance by Patch Clamp in Intact Neurons and Mitochondrial Membrane Preparations. Neuromethods 2017, 123: 211-238. DOI: 10.1007/978-1-4939-6890-9_11.Peer-Reviewed Original ResearchMitochondrial calcium uniporterMitochondrial permeability transition poreInner membraneCell deathOuter membraneIon channelsBcl-2 family proteinsNumerous cellular processesMitochondrial ion channelsComplex of proteinsChannel activityTrafficking of metabolitesPro-death stimuliMitochondrial membrane preparationsPermeability transition poreIon channel activityMembrane compartmentalizationIon channel complexDeath channelATP synthaseCellular processesFamily proteinsCalcium uniporterMolecular participantsATP production
2016
Metabolic Control of Cell Death : The Role of Bcl‐xL
Park H, Licznerski P, Niu Y, Mnatsakanyan N, Miranda P, Wu J, Sacchetti S, Polster B, Alavian K, Jonas E. Metabolic Control of Cell Death : The Role of Bcl‐xL. The FASEB Journal 2016, 30 DOI: 10.1096/fasebj.30.1_supplement.1162.2.Peer-Reviewed Original ResearchΔN-BclMitochondrial permeability transition poreABT-737Glutamate-exposed neuronsBcl-xLGlutamate-induced excitotoxicityGlutamate-induced deathNeuronal energy metabolismMitochondrial potentialCell deathGlutamate challengeBrain ischemiaNeuroprotective propertiesNeuronal survivalFold lower concentrationCyclosporine ASpecific small molecule inhibitorsATP productionSmall molecule inhibitorsMetabolic controlMitochondrial channel activityMalignant cellsPro-apoptotic roleNeuronsDeathPhysiological 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 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
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