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
2022
CAV2.3 expression is upregulated in the substantia nigra pars compacta of humans with Parkinson's disease
Sharifi P, Bae H, Gveric D, Gentleman S, Smith P, Tierney T, Alavian K. CAV2.3 expression is upregulated in the substantia nigra pars compacta of humans with Parkinson's disease. Brain Disorders 2022, 5: 100031. DOI: 10.1016/j.dscb.2022.100031.Peer-Reviewed Original ResearchInitial experience with magnetic resonance-guided focused ultrasound stereotactic surgery for central brain lesions in young adults.
Tierney T, Alavian K, Altman N, Bhatia S, Duchowny M, Hyslop A, Jayakar P, Resnick T, Wang S, Miller I, Ragheb J. Initial experience with magnetic resonance-guided focused ultrasound stereotactic surgery for central brain lesions in young adults. Journal Of Neurosurgery 2022, 137: 760-767. PMID: 35171812, DOI: 10.3171/2021.10.jns21416.Peer-Reviewed Original ResearchSubependymal giant cell astrocytomaHypothalamic hamartomaBrain lesionsIntracranial lesionsYoung adultsNew neurological deficitsPostoperative day 1Procedure-related complicationsLong-term outcomesMagnetic resonance-guided focused ultrasoundSingle-arm trialCases of hemorrhageGiant cell astrocytomaTreatment of tremorNicklaus Children's HospitalTuberous sclerosis complexYears of ageYoung adult populationCentral brain lesionsPatients 15Neurological deficitsSeizure controlPostoperative MRIPrimary outcomeElectrolyte derangements
2021
Threshold Concepts in Neuroscience: Identification Challenges, Educational Opportunities and Recommendations for Practice
Sandrone S, Alavian K. Threshold Concepts in Neuroscience: Identification Challenges, Educational Opportunities and Recommendations for Practice. Frontiers In Education 2021, 5: 540307. DOI: 10.3389/feduc.2020.540307.Peer-Reviewed Original ResearchThe factors for the early and late development of midbrain dopaminergic neurons segregate into two distinct evolutionary clusters
Niu Y, Moghimyfiroozabad S, Moghimyfiroozabad A, Tierney T, Alavian K. The factors for the early and late development of midbrain dopaminergic neurons segregate into two distinct evolutionary clusters. Brain Disorders 2021, 1: 100002. DOI: 10.1016/j.dscb.2021.100002.Peer-Reviewed Original ResearchTranscription factorsNon-canonical functionsMidbrain dopaminergic neuronsDistinct evolutionary pathwaysEntire human proteomeNovel molecular connectionDopaminergic neuronsPotential novel linkPhylogenetic profilesEvolutionary pathwaysHuman proteomeEvolutionary scenarioMolecular connectionEvolutionary clustersDevelopmental pathwaysNovel linkNeuronal differentiationNovel linkageDevelopmental cascadeParkinson's diseasePathwayNeuronsMotor behaviorControl of emotionsProteomeDisorders of the brain, paradoxes of the enigma
Alavian K, Yu J. Disorders of the brain, paradoxes of the enigma. Brain Disorders 2021, 1: 100003. DOI: 10.1016/j.dscb.2021.100003.Peer-Reviewed Original Research
2020
Mitochondrial (ATP Synthase) Permeability Transition Pore
Jonas E, Mnatsakanyan N, Alavian K, Chen R. Mitochondrial (ATP Synthase) Permeability Transition Pore. Biophysical Journal 2020, 118: 16a. DOI: 10.1016/j.bpj.2019.11.269.Peer-Reviewed Original Research
2019
Post mortem examination of Parkinson's disease brains suggests decline in mitochondrial biomass, reversed by deep brain stimulation of subthalamic nucleus
Mallach A, Weinert M, Arthur J, Gveric D, Tierney TS, Alavian KN. Post mortem examination of Parkinson's disease brains suggests decline in mitochondrial biomass, reversed by deep brain stimulation of subthalamic nucleus. The FASEB Journal 2019, 33: 6957-6961. PMID: 30862197, DOI: 10.1096/fj.201802628r.Peer-Reviewed Original ResearchConceptsDeep brain stimulationParkinson's disease brainSubthalamic nucleusParkinson's diseaseDisease brainBrain stimulationPresynaptic terminalsSNpc neuronsEffects of DBSLong-term clinical benefitSubstantia nigra pars compactaLate-stage patientsMitochondrial biomassDA neuronsSTN-DBSSurgical treatmentNeuroprotective effectsPars compactaClinical benefitDA projectionsPD brainsDopaminergic neuronsDBS treatmentNeuromodulatory effectsPD cases
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 transportMitochondria and Memory: Bioenergetics, Synaptic Plasticity and Neurodegeneration
Jonas E, Mnatsakanyan N, Miranda P, Park H, Chen R, Licznerski P, Weinert M, Smith P, Chavez A, Zukin R, Gribkoff V, Alavian K. Mitochondria and Memory: Bioenergetics, Synaptic Plasticity and Neurodegeneration. Biophysical Journal 2017, 112: 180a. DOI: 10.1016/j.bpj.2016.11.996.Peer-Reviewed Original Research
2016
The Mitochondrial Permeability Transition Pore and ATP Synthase
Beutner G, Alavian K, Jonas EA, Porter GA. The Mitochondrial Permeability Transition Pore and ATP Synthase. Handbook Of Experimental Pharmacology 2016, 240: 21-46. PMID: 27590224, PMCID: PMC7439278, DOI: 10.1007/164_2016_5.BooksConceptsPermeability transition poreElectron transport chainATP synthaseGeneration of ATPMitochondrial permeability transition poreATP generationTransition poreCell deathC subunit ringMitochondrial ATP generationFo subunitsEmbryonic mouse heartPTP openingTransport chainOxidative phosphorylationEquivalents NADHMature cellsSynthasePhysiologic roleMouse heartsATPRecent studiesPhosphorylationSubunitsFADH2PTP and LTP: The physiological role of the permeability transition pore in learning and memory
Jonas E, Miranda P, Gribkoff V, Alavian K, Park H, Wu J, Chavez A, Zukin R, Hardwick J, Mnatsakanyan N. PTP and LTP: The physiological role of the permeability transition pore in learning and memory. Biochimica Et Biophysica Acta (BBA) - Bioenergetics 2016, 1857: e66-e67. DOI: 10.1016/j.bbabio.2016.04.357.Peer-Reviewed Original ResearchMetabolic 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
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 productionABT‐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 activityAnalysis of Gene Expression Changes in the Rat Hippocampus After Deep Brain Stimulation of the Anterior Thalamic Nucleus
Selvakumar T, Alavian K, Tierney T. Analysis of Gene Expression Changes in the Rat Hippocampus After Deep Brain Stimulation of the Anterior Thalamic Nucleus. Journal Of Visualized Experiments 2015 DOI: 10.3791/52457-v.Peer-Reviewed Original ResearchIsolation, Culture and Long-Term Maintenance of Primary Mesencephalic Dopaminergic Neurons From Embryonic Rodent Brains
Weinert M, Selvakumar T, Tierney T, Alavian K. Isolation, Culture and Long-Term Maintenance of Primary Mesencephalic Dopaminergic Neurons From Embryonic Rodent Brains. Journal Of Visualized Experiments 2015 DOI: 10.3791/52475-v.Peer-Reviewed Original Research
2014
The C-Subunit of the ATP Synthase Forms the Pore of the PTP
Jonas E, Sacchetti S, Park H, Lazrove E, Beutner G, Porter G, Alavian K. The C-Subunit of the ATP Synthase Forms the Pore of the PTP. Biophysical Journal 2014, 106: 3a-4a. DOI: 10.1016/j.bpj.2013.11.049.Peer-Reviewed Original Research
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 neuronsComplexesF<sub>1</sub>F<sub>O</sub> ATPase Vesicle Preparation and Technique for Performing Patch Clamp Recordings of Submitochondrial Vesicle Membranes
Sacchetti S, Alavian K, Lazrove E, Jonas E. F1FO ATPase Vesicle Preparation and Technique for Performing Patch Clamp Recordings of Submitochondrial Vesicle Membranes. Journal Of Visualized Experiments 2013 DOI: 10.3791/4394-v.Peer-Reviewed Original Research