2019
Mitochondrial unfolded protein response: a stress response with implications for fertility and reproductive aging
Seli E, Wang T, Horvath TL. Mitochondrial unfolded protein response: a stress response with implications for fertility and reproductive aging. Fertility And Sterility 2019, 111: 197-204. PMID: 30691623, DOI: 10.1016/j.fertnstert.2018.11.048.Peer-Reviewed Original ResearchConceptsMitochondrial unfolded protein responseTwo-cell embryo developmentUnfolded protein responseImpaired oocyte maturationMorphology of mitochondriaMitochondrial dysfunction resultsPremature reproductive agingNovel mechanistic insightsMitochondrial DNA contentReactive oxygen species productionPrevention of agingCLPP resultsProtein responseOxygen species productionReproductive agingPreimplantation embryosAge-related accumulationOxidative phosphorylationStress responseEmbryo developmentForm blastocystsMitochondrial functionMitochondriaMitochondrial dysfunctionEnergy metabolism
2013
UCP2 overexpression worsens mitochondrial dysfunction and accelerates disease progression in a mouse model of amyotrophic lateral sclerosis
Peixoto PM, Kim HJ, Sider B, Starkov A, Horvath TL, Manfredi G. UCP2 overexpression worsens mitochondrial dysfunction and accelerates disease progression in a mouse model of amyotrophic lateral sclerosis. Molecular And Cellular Neuroscience 2013, 57: 104-110. PMID: 24141050, PMCID: PMC3891658, DOI: 10.1016/j.mcn.2013.10.002.Peer-Reviewed Original ResearchConceptsAmyotrophic lateral sclerosisDouble transgenic miceFamilial amyotrophic lateral sclerosisMouse modelLateral sclerosisMitochondrial dysfunctionTransgenic miceMutant SOD1 mouse modelHuman UCP2Brain mitochondriaSOD1 mutant miceUCP2 overexpressionPotential neuroprotective effectsProtection of neuronsSOD1 mouse modelCentral nervous systemReactive oxygen species productionDisease courseG93A miceNeuroprotective effectsNeuroprotective roleFree radical generationDisease progressionOxygen species productionInjury paradigms
2009
Ghrelin Promotes and Protects Nigrostriatal Dopamine Function via a UCP2-Dependent Mitochondrial Mechanism
Andrews ZB, Erion D, Beiler R, Liu ZW, Abizaid A, Zigman J, Elsworth JD, Savitt JM, DiMarchi R, Tschöp M, Roth RH, Gao XB, Horvath TL. Ghrelin Promotes and Protects Nigrostriatal Dopamine Function via a UCP2-Dependent Mitochondrial Mechanism. Journal Of Neuroscience 2009, 29: 14057-14065. PMID: 19906954, PMCID: PMC2845822, DOI: 10.1523/jneurosci.3890-09.2009.Peer-Reviewed Original ResearchConceptsDA cell lossNigrostriatal dopamine functionParkinson's diseaseDopamine functionCell lossSubstantia nigra pars compactaSNpc DA neuronsStriatal dopamine levelsStriatal dopamine lossExogenous ghrelin administrationLoss of appetiteDopamine cell degenerationNovel therapeutic strategiesMitochondrial mechanismsTyrosine hydroxylase mRNAReactive oxygen species productionMPTP treatmentPeripheral ghrelinSNpc cellsTetrahydropyridine (MPTP) treatmentDA neuronsDopamine lossGhrelin administrationPars compactaCatecholaminergic neuronsUncoupling protein-2 regulates lifespan in mice
Andrews ZB, Horvath TL. Uncoupling protein-2 regulates lifespan in mice. AJP Endocrinology And Metabolism 2009, 296: e621-e627. PMID: 19141680, PMCID: PMC2670629, DOI: 10.1152/ajpendo.90903.2008.Peer-Reviewed Original ResearchConceptsDifferent tissuesProtein 2Uncoupled mitochondrial respirationReactive oxygen species productionMammalian physiologyMutant animalsOxygen species productionMitochondrial respirationLevels of UCP2Species productionTissue functionLong lifespanUCP2Oxidative stressLifespanPostnatal survivalWild-type miceMiceTissuePhysiologyRespirationCells
2006
Uncoupling protein 2/3 immunoreactivity and the ascending dopaminergic and noradrenergic neuronal systems: Relevance for volume transmission
Rivera A, Agnati LF, Horvath TL, Valderrama JJ, de La Calle A, Fuxe K. Uncoupling protein 2/3 immunoreactivity and the ascending dopaminergic and noradrenergic neuronal systems: Relevance for volume transmission. Neuroscience 2006, 137: 1447-1461. PMID: 16387447, DOI: 10.1016/j.neuroscience.2005.05.051.Peer-Reviewed Original ResearchConceptsConfocal laser microscopy analysisReactive oxygen species productionLaser microscopy analysisProtein 2/3Oxygen species productionUncouple oxidative phosphorylationOxidative phosphorylationATP synthesisProteinSpecies productionDouble immunolabelingImportant roleMicroscopy analysisPhosphorylationMitochondriaRegulationCell groupsPlastic changesLocalizationIslandsAnimal modelsMagnaTyrosine hydroxylaseNeuronal systems
2005
Mitochondrial uncoupling proteins in the cns: in support of function and survival
Andrews ZB, Diano S, Horvath TL. Mitochondrial uncoupling proteins in the cns: in support of function and survival. Nature Reviews Neuroscience 2005, 6: 829-840. PMID: 16224498, DOI: 10.1038/nrn1767.Peer-Reviewed Original ResearchConceptsNeuronal functionNeurological disordersTraumatic brain injuryAmyotrophic lateral sclerosisClinical treatment strategiesMitochondrial calcium influxModels of neurodegenerationMitochondrial uncouplingFree radical productionReactive oxygen species productionNeuronal deteriorationNeuronal deathSubstantia nigraBrain injurySpinal cordVentral tegmentumTreatment strategiesOxygen species productionNeuronal microenvironmentSynaptic transmissionCalcium influxLimbic systemNeurological conditionsLateral sclerosisParkinson's diseaseUncoupling Protein-2 Is Critical for Nigral Dopamine Cell Survival in a Mouse Model of Parkinson's Disease
Andrews ZB, Horvath B, Barnstable CJ, Elseworth J, Yang L, Beal MF, Roth RH, Matthews RT, Horvath TL. Uncoupling Protein-2 Is Critical for Nigral Dopamine Cell Survival in a Mouse Model of Parkinson's Disease. Journal Of Neuroscience 2005, 25: 184-191. PMID: 15634780, PMCID: PMC6725213, DOI: 10.1523/jneurosci.4269-04.2005.Peer-Reviewed Original ResearchMeSH Keywords1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine1-Methyl-4-phenylpyridiniumAnimalsCell SurvivalCorpus StriatumDisease Models, AnimalDopamineHumansImmunohistochemistryIon ChannelsMaleMembrane Transport ProteinsMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMitochondriaMitochondrial ProteinsOxygen ConsumptionParkinsonian DisordersReactive Oxygen SpeciesSubstantia NigraUncoupling Protein 2ConceptsProtein 2Mitochondrial ROS productionLack of UCP2Reactive oxygen species productionGenetic manipulationOxygen species productionMitochondria numberCell metabolismATP synthesisCell survivalOverexpression of UCP2Wild-type controlsMitochondrial uncouplingNovel therapeutic targetROS productionUCP2Species productionElectron microscopic analysisOverexpressionCell functionUCP2 overexpressionDopamine cell survivalTherapeutic targetFluorescent ethidiumDopamine cell function