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 leakMaturationMetabolism
2011
Bcl-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
2008
Bcl-xL induces Drp1-dependent synapse formation in cultured hippocampal neurons
Li H, Chen Y, Jones AF, Sanger RH, Collis LP, Flannery R, McNay EC, Yu T, Schwarzenbacher R, Bossy B, Bossy-Wetzel E, Bennett MV, Pypaert M, Hickman JA, Smith PJ, Hardwick JM, Jonas EA. Bcl-xL induces Drp1-dependent synapse formation in cultured hippocampal neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 2169-2174. PMID: 18250306, PMCID: PMC2542873, DOI: 10.1073/pnas.0711647105.Peer-Reviewed Original ResearchConceptsBcl-xL proteinBcl-xLVesicle clustersDynamin-related protein 1Synapse formationOverexpression of Drp1Mitochondrial fission proteinSynaptic vesicle clustersMitochondrial localizationFission proteinsGTPase activityDrp1Cultured hippocampal neuronsMitochondrial functionHippocampal neuronsNeuronal synapsesRecombinant systemsABT-737Protein 1ProteinTissue lysatesAdult neuronsSpontaneous miniature synaptic currentsOverexpressionMiniature synaptic currents
2006
BCL-xL regulates synaptic plasticity.
Jonas E. BCL-xL regulates synaptic plasticity. Molecular Interventions 2006, 6: 208-22. PMID: 16960143, DOI: 10.1124/mi.6.4.7.Peer-Reviewed Original ResearchConceptsBcl-xLSynaptic vesicle recyclingRole of mitochondriaHigh synaptic activityMembrane ion pumpsMitochondrial localizationCalcium homeostasisVesicle recyclingPresynaptic terminalsPredominant organellesCell deathSynaptic vesiclesSynaptic developmentIon pumpsIntracellular calcium homeostasisRecent discoveryMitochondriaSynaptic transmitter releaseHomeostasisSynaptic plasticitySynaptic sitesSynapseSynaptic processesSynaptic activityOrganelles
2005
Actions of BAX on Mitochondrial Channel Activity and on Synaptic Transmission
Jonas EA, Hardwick JM, Kaczmarek LK. Actions of BAX on Mitochondrial Channel Activity and on Synaptic Transmission. Antioxidants & Redox Signaling 2005, 7: 1092-1100. PMID: 16115013, DOI: 10.1089/ars.2005.7.1092.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBcl-2-Associated X ProteinBcl-X ProteinCell MembraneElectrophysiologyIntracellular MembranesLiposomesLoligoMitochondriaMultigene FamilyNeurotransmitter AgentsPatch-Clamp TechniquesPeptidesPresynaptic TerminalsProtein Structure, TertiarySynapsesSynaptic TransmissionTime FactorsConceptsMitochondrial membraneBcl-2 family proteins BaxCell deathOuter mitochondrial membraneAction of BaxMitochondrial channel activityChannel activityNormal physiological settingsAntiapoptotic Bcl-xL proteinBcl-xL proteinDeath channelMitochondrial architectureMitochondrial channelsProapoptotic fragmentsLarge conductance channelPresynaptic terminalsBcl-xL.Proapoptotic proteinsAlternative functionsProtein BaxPhysiological settingsPhysiological roleSynaptic transmissionBaxNeurotransmitter release
2004
Exposure to Hypoxia Rapidly Induces Mitochondrial Channel Activity within a Living Synapse*
Jonas EA, Hickman JA, Hardwick JM, Kaczmarek LK. Exposure to Hypoxia Rapidly Induces Mitochondrial Channel Activity within a Living Synapse*. Journal Of Biological Chemistry 2004, 280: 4491-4497. PMID: 15561723, DOI: 10.1074/jbc.m410661200.Peer-Reviewed Original ResearchConceptsMitochondrial channel activityMitochondrial membraneChannel activityBcl-xLBcl-2 family proteinsPro-apoptotic fragmentsOuter mitochondrial membraneTrigger cell deathZ-VAD-FMKBenzyloxycarbonyl-VADFamily proteinsSynaptic responsesMulticonductance channelLarge conductance channelFluoromethyl ketoneCell deathMinutes of hypoxiaResponses of neuronsNeuronal functionSquid giant synapseSynaptic mitochondriaEarly eventsSynaptic functionHypoxic conditionsNeuronal death