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 roleNeuronsDeath
2015
ABT‐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
2013
A Bcl-xL–Drp1 complex regulates synaptic vesicle membrane dynamics during endocytosis
Li H, Alavian KN, Lazrove E, Mehta N, Jones A, Zhang P, Licznerski P, Graham M, Uo T, Guo J, Rahner C, Duman RS, Morrison RS, Jonas EA. A Bcl-xL–Drp1 complex regulates synaptic vesicle membrane dynamics during endocytosis. Nature Cell Biology 2013, 15: 773-785. PMID: 23792689, PMCID: PMC3725990, DOI: 10.1038/ncb2791.Peer-Reviewed Original ResearchConceptsBcl-xLVesicle retrievalProtein-protein interactionsClathrin-coated pitsProtein Bcl-xLCalmodulin-dependent mannerRecruitment of vesiclesNeurotransmitter releaseDepletion of Drp1GTPase Drp1Vesicle endocytosisEndocytic vesiclesMembrane dynamicsPlasma membraneClathrin complexMutagenesis studiesPresynaptic plasticityMitochondrial ATPATP availabilityReserve poolDrp1EndocytosisVesiclesHippocampal neuronsComplexes
2012
N-terminally cleaved Bcl-xL mediates ischemia-induced neuronal death
Ofengeim D, Chen YB, Miyawaki T, Li H, Sacchetti S, Flannery RJ, Alavian KN, Pontarelli F, Roelofs BA, Hickman JA, Hardwick JM, Zukin RS, Jonas EA. N-terminally cleaved Bcl-xL mediates ischemia-induced neuronal death. Nature Neuroscience 2012, 15: 574-580. PMID: 22366758, PMCID: PMC3862259, DOI: 10.1038/nn.3054.Peer-Reviewed Original Research
2011
Bcl-xL regulates mitochondrial energetics by stabilizing the inner membrane potential
Chen YB, Aon MA, Hsu YT, Soane L, Teng X, McCaffery JM, Cheng WC, Qi B, Li H, Alavian KN, Dayhoff-Brannigan M, Zou S, Pineda FJ, O'Rourke B, Ko YH, Pedersen PL, Kaczmarek LK, Jonas EA, Hardwick JM. Bcl-xL regulates mitochondrial energetics by stabilizing the inner membrane potential. Journal Of Cell Biology 2011, 195: 263-276. PMID: 21987637, PMCID: PMC3198165, DOI: 10.1083/jcb.201108059.Peer-Reviewed Original ResearchConceptsMitochondrial membrane potentialMitochondrial membraneMitochondrial ATP synthase β-subunitATP synthase β subunitBcl-2 family proteinsOuter membrane permeabilizationInner mitochondrial membrane potentialMembrane potentialMitochondrial energetic capacityOuter mitochondrial membraneSynthase β subunitInner mitochondrial membraneInner membrane potentialATP synthaseFamily proteinsBiochemical approachesGenetic evidenceEndogenous BclMembrane permeabilizationCellular resourcesΒ-subunitBcl-xLMitochondrial energeticsEnergetic capacityMitochondrial cristaeBcl-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 moleculesBcl-xL Determines the Metabolic Efficiency of Neurons, through Interaction with Mitochondrial ATP Synthase
Alavian K, Li H, Sacchetti S, Nabili P, Lazrove E, Bonanni L, Smith P, Hardwick J, Jonas E. Bcl-xL Determines the Metabolic Efficiency of Neurons, through Interaction with Mitochondrial ATP Synthase. Biophysical Journal 2011, 100: 459a. DOI: 10.1016/j.bpj.2010.12.2700.Peer-Reviewed Original Research