2022
Plant mitochondrial FMT and its mammalian homolog CLUH controls development and behavior in Arabidopsis and locomotion in mice
Ralevski A, Apelt F, Olas JJ, Mueller-Roeber B, Rugarli EI, Kragler F, Horvath TL. Plant mitochondrial FMT and its mammalian homolog CLUH controls development and behavior in Arabidopsis and locomotion in mice. Cellular And Molecular Life Sciences 2022, 79: 334. PMID: 35652974, PMCID: PMC11071973, DOI: 10.1007/s00018-022-04382-3.Peer-Reviewed Original ResearchConceptsMitochondrial genesWhole plant morphologySalt stress responseNormal growth conditionsLeaf expansion growthArabidopsis thalianaHigher eukaryotesGene familyMitochondrial proteinsPlant morphologyHomologous functionsMitochondrial morphologyExpansion growthStress responseMitochondrial functionAnimal speciesPlantsSimilar roleGrowth conditionsHeterozygous knockout miceGenesDevelopmental alterationsKnockout miceCLUHArabidopsis
2021
Mitochondrial cristae-remodeling protein OPA1 in POMC neurons couples Ca2+ homeostasis with adipose tissue lipolysis
Gómez-Valadés AG, Pozo M, Varela L, Boudjadja MB, Ramírez S, Chivite I, Eyre E, Haddad-Tóvolli R, Obri A, Milà-Guasch M, Altirriba J, Schneeberger M, Imbernón M, Garcia-Rendueles AR, Gama-Perez P, Rojo-Ruiz J, Rácz B, Alonso MT, Gomis R, Zorzano A, D’Agostino G, Alvarez CV, Nogueiras R, Garcia-Roves PM, Horvath TL, Claret M. Mitochondrial cristae-remodeling protein OPA1 in POMC neurons couples Ca2+ homeostasis with adipose tissue lipolysis. Cell Metabolism 2021, 33: 1820-1835.e9. PMID: 34343501, PMCID: PMC8432968, DOI: 10.1016/j.cmet.2021.07.008.Peer-Reviewed Original ResearchConceptsProtein OPA1Mitochondrial CaMitochondrial cristae architectureAdipose tissue lipolysisKey metabolic sensorPOMC neuronsCellular metabolic adaptationTissue lipolysisCristae architectureMetabolic sensorNutrient availabilityWhite adipose tissue lipolysisAlpha-melanocyte stimulating hormoneGenetic inactivationNovel axisMitochondrial functionOPA1Metabolic adaptationMitochondrial cristaeDramatic alterationsMutant miceProopiomelanocortin neuronsLipolysis controlWAT lipolysisPharmacological blockade
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
2018
Metabolic regulation and glucose sensitivity of cortical radial glial cells
Rash BG, Micali N, Huttner AJ, Morozov YM, Horvath TL, Rakic P. Metabolic regulation and glucose sensitivity of cortical radial glial cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: 10142-10147. PMID: 30224493, PMCID: PMC6176632, DOI: 10.1073/pnas.1808066115.Peer-Reviewed Original ResearchConceptsRadial glial cellsGlial cellsRGC fibersCortical radial glial cellsEmbryonic cortical slicesGestational obesityCerebral cortexCortical slicesMetabolic disturbancesCortical neurogenesisMetabolic supportBrain disordersAcute lossMitochondrial transportBrain developmentIntracellular CaPotential mechanismsHyperglycemiaMitochondrial functionGlucose sensitivityMiceStem cellsPrimary stem cellsPhysiological mechanismsCellsMitochondrial unfolded protein response gene Clpp is required to maintain ovarian follicular reserve during aging, for oocyte competence, and development of pre‐implantation embryos
Wang T, Babayev E, Jiang Z, Li G, Zhang M, Esencan E, Horvath T, Seli E. Mitochondrial unfolded protein response gene Clpp is required to maintain ovarian follicular reserve during aging, for oocyte competence, and development of pre‐implantation embryos. Aging Cell 2018, 17: e12784. PMID: 29851234, PMCID: PMC6052477, DOI: 10.1111/acel.12784.Peer-Reviewed Original ResearchConceptsMitochondrial unfolded protein responseUnfolded mitochondrial proteinsCaseinolytic peptidase PAbsence of ClpPUnfolded protein responsePre-implantation embryosExpression of genesOocyte mitochondrial functionTwo-cell embryosProtein homeostasisMTOR inhibitor rapamycinMitochondrial proteinsOocyte competenceClpPProtein responseInhibitor rapamycinMitochondrial functionP-Akt473P-S6KOvarian follicular reserveSmall mitochondriaMTOR pathway activationPathway activationEmbryosP-S6
2016
Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability
García-Cáceres C, Quarta C, Varela L, Gao Y, Gruber T, Legutko B, Jastroch M, Johansson P, Ninkovic J, Yi CX, Le Thuc O, Szigeti-Buck K, Cai W, Meyer CW, Pfluger PT, Fernandez AM, Luquet S, Woods SC, Torres-Alemán I, Kahn CR, Götz M, Horvath TL, Tschöp MH. Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability. Cell 2016, 166: 867-880. PMID: 27518562, PMCID: PMC8961449, DOI: 10.1016/j.cell.2016.07.028.Peer-Reviewed Original ResearchConceptsBlood-brain barrierSystemic glucose metabolismInsulin receptorGlucose metabolismGlucose uptakeGlial fibrillary acidic proteinBrain glucose uptakePostnatal ablationHypothalamic glucose sensingGlutamate-aspartate transporterFibrillary acidic proteinPositron emission tomographyMelanocortin neuronsKO miceGlucose levelsAstrocyte morphologyNormal responseEmission tomographyGlucose-induced activationAcidic proteinAspartate transporterCircuit connectivityInsulinGlucose availabilityMitochondrial functionRole of mitochondrial uncoupling protein-2 (UCP2) in higher brain functions, neuronal plasticity and network oscillation
Hermes G, Nagy D, Waterson M, Zsarnovszky A, Varela L, Hajos M, Horvath TL. Role of mitochondrial uncoupling protein-2 (UCP2) in higher brain functions, neuronal plasticity and network oscillation. Molecular Metabolism 2016, 5: 415-421. PMID: 27257601, PMCID: PMC4877662, DOI: 10.1016/j.molmet.2016.04.002.Peer-Reviewed Original ResearchMouse modelSynaptic plasticityMental illnessUCP2 knockout miceNMDA receptor blockadeHigher brain regionsKO mouse modelMajor psychiatric illnessProtein 2 expressionHigher brain functionsReceptor blockadePsychiatric illnessNeuronal plasticityKnockout miceNeural transmissionCellular resilienceCortical activityBrain regionsProfound disorderBrain functionMitochondrial impairmentIllnessNetwork oscillationsMitochondrial functionProtein 2
2013
Antibodies to cannabinoid type 1 receptor co‐react with stomatin‐like protein 2 in mouse brain mitochondria
Morozov YM, Dominguez MH, Varela L, Shanabrough M, Koch M, Horvath TL, Rakic P. Antibodies to cannabinoid type 1 receptor co‐react with stomatin‐like protein 2 in mouse brain mitochondria. European Journal Of Neuroscience 2013, 38: 2341-2348. PMID: 23617247, PMCID: PMC3902808, DOI: 10.1111/ejn.12237.Peer-Reviewed Original ResearchConceptsStomatin-like protein 2Type 1 receptorPresence of CB1Protein 2Anti-CB1 antibodySynthetic cannabinoid WINMouse brain mitochondriaCerebral cortexEndocannabinoid signalingBrain cellsCannabinoid WINNeuronal mitochondriaBrain mitochondriaAntibodiesMitochondrial functionCB1Polyclonal antibodiesCortexMitochondrial preparationsSerumReceptors
2011
GPA protects the nigrostriatal dopamine system by enhancing mitochondrial function
Horvath TL, Erion DM, Elsworth JD, Roth RH, Shulman GI, Andrews ZB. GPA protects the nigrostriatal dopamine system by enhancing mitochondrial function. Neurobiology Of Disease 2011, 43: 152-162. PMID: 21406233, PMCID: PMC3623269, DOI: 10.1016/j.nbd.2011.03.005.Peer-Reviewed Original ResearchConceptsNormal chow-fed miceNigrostriatal dopamine systemChow-fed miceTH neuronsGuanidinopropionic acidNormal chowParkinson's diseaseDopamine systemMitochondrial functionMitochondrial dysfunctionModels of neurodegenerationMitochondrial numberAMPK activityMPTP treatmentMPTP intoxicationNigrostriatal functionNeuroprotective effectsMitochondrial respirationNeuroprotective propertiesStriatal dopamineAMPK-dependent increaseDisease progressionMouse modelMiceMPTP