2019
Mitofusin 2 plays a role in oocyte and follicle development, and is required to maintain ovarian follicular reserve during reproductive aging
Zhang M, Bener MB, Jiang Z, Wang T, Esencan E, Scott R, Horvath T, Seli E. Mitofusin 2 plays a role in oocyte and follicle development, and is required to maintain ovarian follicular reserve during reproductive aging. Aging 2019, 11: 3919-3938. PMID: 31204316, PMCID: PMC6628992, DOI: 10.18632/aging.102024.Peer-Reviewed Original ResearchConceptsMitofusin 2Key regulatory proteinsImpaired oocyte maturationFollicle developmentMitochondrial fusionRegulatory proteinsEndoplasmic reticulumMitochondrial dysfunctionTargeted deletionOocyte maturationOocytesReproductive agingFemale subfertilityOocyte qualityOvarian follicular reserveTelomeresMitochondriaMetabolic milieuProteinReticulumDeletionFusionPhenotypeApoptosisMaturation
2016
Reproductive aging is associated with changes in oocyte mitochondrial dynamics, function, and mtDNA quantity
Babayev E, Wang T, Szigeti-Buck K, Lowther K, Taylor HS, Horvath T, Seli E. Reproductive aging is associated with changes in oocyte mitochondrial dynamics, function, and mtDNA quantity. Maturitas 2016, 93: 121-130. PMID: 27523387, PMCID: PMC5064871, DOI: 10.1016/j.maturitas.2016.06.015.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsDNA, MitochondrialFemaleHydrogen PeroxideMiceMice, Inbred C57BLMitochondriaMitochondrial DynamicsOocytesReactive Oxygen SpeciesReproductionConceptsReactive oxygen speciesUnfolded protein response genesProtein response genesMitochondrial DNAMitochondrial dynamicsMitochondrial stressResponse genesMammalian reproductionMitochondria morphologyStressful conditionsMitochondrial changesMitochondriaROS levelsMtDNA levelsElevated expressionMtDNA quantityOxygen speciesOocytesGenesMature oocytesNumerous aspectsExpressionReproductive agingMII oocytesFollicle-enclosed oocytes
2015
Mitochondrial ROS Signaling in Organismal Homeostasis
Shadel GS, Horvath TL. Mitochondrial ROS Signaling in Organismal Homeostasis. Cell 2015, 163: 560-569. PMID: 26496603, PMCID: PMC4634671, DOI: 10.1016/j.cell.2015.10.001.Peer-Reviewed Original ResearchConceptsReactive oxygen speciesOrganismal homeostasisMitochondrial ROS signalingMitochondrial reactive oxygen speciesAdaptive physiological responsesROS signalingCellular differentiationMitochondrial oxygen consumptionOxidative phosphorylationPhysiological responsesOxygen speciesCentral roleHomeostasisEukaryotesOrganic fuel moleculesPhosphorylationMitochondriaMoleculesSignalingSpeciesATPDifferentiationPathwayGreater understandingRole
2014
PPARγ ablation sensitizes proopiomelanocortin neurons to leptin during high-fat feeding
Long L, Toda C, Jeong JK, Horvath TL, Diano S. PPARγ ablation sensitizes proopiomelanocortin neurons to leptin during high-fat feeding. Journal Of Clinical Investigation 2014, 124: 4017-4027. PMID: 25083994, PMCID: PMC4151211, DOI: 10.1172/jci76220.Peer-Reviewed Original ResearchConceptsHigh-fat dietPOMC neuronsFood intakeImproved glucose metabolismHigh-fat feedingWhole-body energy balanceBody weight gainProopiomelanocortin neuronsPeripheral administrationFat massLeptin sensitivityControl animalsGlucose metabolismBody weightPPARγ activatorsLocomotor activityEnergy homeostasisPPARγWeight gainNeuronsSelective ablationEnergy expenditureIntakeNuclear receptorsMice
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 paradigmsRole of uncoupling protein 3 in ischemia-reperfusion injury, arrhythmias, and preconditioning
Ozcan C, Palmeri M, Horvath TL, Russell KS, Russell RR. Role of uncoupling protein 3 in ischemia-reperfusion injury, arrhythmias, and preconditioning. AJP Heart And Circulatory Physiology 2013, 304: h1192-h1200. PMID: 23457013, PMCID: PMC3652089, DOI: 10.1152/ajpheart.00592.2012.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsArrhythmias, CardiacCarbonyl Cyanide p-TrifluoromethoxyphenylhydrazoneCoronary OcclusionIn Vitro TechniquesIon ChannelsIschemic Preconditioning, MyocardialMaleMiceMice, Inbred C57BLMitochondrial ProteinsMyocardial InfarctionMyocardial Reperfusion InjuryMyocytes, CardiacReactive Oxygen SpeciesUncoupling Protein 2Uncoupling Protein 3Ventricular DysfunctionConceptsIschemia-reperfusion injuryR injuryIschemic preconditioningWT heartsMyocardial energeticsMouse heartsReactive oxygen speciesLeft coronary arteryLeft ventricular functionPostischemic functional recoveryWild-type mouse heartsUncoupling proteinDecreased ATP contentR arrhythmiasLarge infarctsVentricular functionFunctional recoveryWT miceCoronary arteryProtective efficacyCardioprotective efficacyMyocardial vulnerabilityVivo modelInjuryRole of UCPs
2011
Mitochondrial uncoupling protein 2 (UCP2) in glucose and lipid metabolism
Diano S, Horvath TL. Mitochondrial uncoupling protein 2 (UCP2) in glucose and lipid metabolism. Trends In Molecular Medicine 2011, 18: 52-58. PMID: 21917523, DOI: 10.1016/j.molmed.2011.08.003.Peer-Reviewed Original ResearchConceptsProtein 2Lipid metabolismExcess of nutrientsHypothalamic neuronal circuitsNutrient availabilityPeripheral tissue functionsPhysiological functionsMetabolism regulationChronic diseasesMetabolism-related chronic diseasesTissue functionFuture therapeutic strategiesPathological processesPeripheral mechanismsLipid levelsNeuronal circuitsTherapeutic strategiesMetabolismImpairs healthMitochondriaDiseaseUCP2GlucoseRegulationNutrientsPeroxisome proliferation–associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity
Diano S, Liu ZW, Jeong JK, Dietrich MO, Ruan HB, Kim E, Suyama S, Kelly K, Gyengesi E, Arbiser JL, Belsham DD, Sarruf DA, Schwartz MW, Bennett AM, Shanabrough M, Mobbs CV, Yang X, Gao XB, Horvath TL. Peroxisome proliferation–associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity. Nature Medicine 2011, 17: 1121-1127. PMID: 21873987, PMCID: PMC3388795, DOI: 10.1038/nm.2421.Peer-Reviewed Original Research
2009
The role of mitochondrial uncoupling proteins in lifespan
Dietrich MO, Horvath TL. The role of mitochondrial uncoupling proteins in lifespan. Pflügers Archiv - European Journal Of Physiology 2009, 459: 269-275. PMID: 19760284, PMCID: PMC2809791, DOI: 10.1007/s00424-009-0729-0.Peer-Reviewed Original ResearchConceptsMitochondrial inner membraneCellular biochemical reactionsMitochondrial uncoupling proteinProduction of ATPCellular functionsInner membraneSpecialized proteinsBreakdown of lipidsMain organellesExcess of ROSPhysiological uncouplingOxidative phosphorylationUncoupling proteinAdenosine triphosphateOxygen reactive speciesROS productionProteinEnergetic substratesBiochemical reactionsCellular damageMitochondriaROSIntermediate substrateUCPShed lightUncoupling 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
2008
Fuel utilization by hypothalamic neurons: roles for ROS
Horvath TL, Andrews ZB, Diano S. Fuel utilization by hypothalamic neurons: roles for ROS. Trends In Endocrinology And Metabolism 2008, 20: 78-87. PMID: 19084428, DOI: 10.1016/j.tem.2008.10.003.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEatingEnergy MetabolismFoodHumansHungerHypothalamusMelanocortinsModels, BiologicalNeuronsReactive Oxygen SpeciesSatiety ResponseConceptsEnergy homeostasisFree radical productionAnorexigenic neuronsNeuronal doctrineArcuate nucleusHypothalamic neuronsHypothalamic outputMelanocortin systemEffect of glucoseNeuronal functionFree radical formationSpecific neuronsAcid levelsNeuronsAmino acid levelsNeurobiological aspectsRadical productionEvidence pointsFatty acidsFuel sensingIntracellular substratesHomeostasisNutritional signalsGlucoseHypothalamusUCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals
Andrews ZB, Liu ZW, Walllingford N, Erion DM, Borok E, Friedman JM, Tschöp MH, Shanabrough M, Cline G, Shulman GI, Coppola A, Gao XB, Horvath TL, Diano S. UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals. Nature 2008, 454: 846-851. PMID: 18668043, PMCID: PMC4101536, DOI: 10.1038/nature07181.Peer-Reviewed Original ResearchMeSH KeywordsAgouti-Related ProteinAnimalsCarnitine O-PalmitoyltransferaseFatty AcidsFeeding BehaviorGene Expression RegulationGhrelinHypothalamusIon ChannelsMembrane Potential, MitochondrialMiceMitochondriaMitochondrial ProteinsNeuronsNeuropeptide YPhosphorylationReactive Oxygen SpeciesSynapsesUncoupling Protein 2ConceptsNPY/AgRP neuronsAgRP neuronsNeuronal activityCo-express neuropeptide YGut-derived hormone ghrelinAgRP neuronal activityArcuate nucleus neuronsFatty acid oxidation pathwayHypothalamic mitochondrial respirationG protein-coupled receptorsGhrelin actionNeuropeptide YNucleus neuronsHormone ghrelinFood intakeGhrelinFree radicalsSynaptic plasticityNeuronal functionIntracellular mechanismsNeuronsMitochondrial mechanismsProtein 2Mitochondrial proliferationRobust changes
2005
Uncoupling 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