ATP Synthase c-Subunit Leak Causes Aberrant Cellular Metabolism in Fragile X Syndrome
Licznerski P, Park HA, Rolyan H, Chen R, Mnatsakanyan N, Miranda P, Graham M, Wu J, Cruz-Reyes N, Mehta N, Sohail S, Salcedo J, Song E, Effman C, Effman S, Brandao L, Xu GN, Braker A, Gribkoff VK, Levy RJ, Jonas EA. ATP Synthase c-Subunit Leak Causes Aberrant Cellular Metabolism in Fragile X Syndrome. Cell 2020, 182: 1170-1185.e9. PMID: 32795412, PMCID: PMC7484101, DOI: 10.1016/j.cell.2020.07.008.Peer-Reviewed Original ResearchConceptsFragile X syndromeC subunitAberrant synaptic developmentHuman fragile X syndromeATP synthase enzymeMental retardation proteinX syndromeATP production efficiencyMRNA translation rateAberrant cellular metabolismATP synthaseMRNA translationTranslation rateCellular metabolismSynaptic growthSynthase enzymeMouse neuronsSynapse maturationSynaptic developmentPharmacological inhibitionLeak channelsSynaptic maturationMembrane leakMaturationMetabolismInefficient thermogenic mitochondrial respiration due to futile proton leak in a mouse model of fragile X syndrome
Griffiths KK, Wang A, Wang L, Tracey M, Kleiner G, Quinzii CM, Sun L, Yang G, Perez‐Zoghbi J, Licznerski P, Yang M, Jonas EA, Levy RJ. Inefficient thermogenic mitochondrial respiration due to futile proton leak in a mouse model of fragile X syndrome. The FASEB Journal 2020, 34: 7404-7426. PMID: 32307754, PMCID: PMC7692004, DOI: 10.1096/fj.202000283rr.Peer-Reviewed Original ResearchConceptsFragile X syndromeProton leakMental retardation protein (FMRP) expressionInefficient oxidative phosphorylationX syndromeCoenzyme Q deficiencyThermogenic respirationMitochondrial CoQTranscriptional silencingFMRP deficiencyFmr1 knockout miceQ deficiencyDysfunctional mitochondriaFMR1 geneFXS phenotypeOxidative phosphorylationMitochondrial respirationCommon genetic causeProtein synthesisFull mutationKey phenotypicPeak of synaptogenesisMitochondriaProtein expressionGenetic causeParkinson’s disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth
Chen R, Park HA, Mnatsakanyan N, Niu Y, Licznerski P, Wu J, Miranda P, Graham M, Tang J, Boon AJW, Cossu G, Mandemakers W, Bonifati V, Smith PJS, Alavian KN, Jonas EA. Parkinson’s disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth. Cell Death & Disease 2019, 10: 469. PMID: 31197129, PMCID: PMC6565618, DOI: 10.1038/s41419-019-1679-x.Peer-Reviewed Original ResearchConceptsDJ-1C subunitATP synthaseParkinson's disease protein DJ-1Β-subunitProtein componentsATP synthase β subunitMitochondrial uncouplingDJ-1 bindsATP synthase efficiencyATP synthase F1Synthase β subunitATP production efficiencyProtein DJ-1Neuronal process extensionProtein levelsNeuronal process outgrowthDJ-1 knockoutWild-type counterpartsSubunit protein levelsDJ-1 mutationsSevere defectsCell metabolismKO neuronsKO culturesLentivirus-based genetic manipulations of cortical neurons and their optical and electrophysiological monitoring in vivo
Dittgen T, Nimmerjahn A, Komai S, Licznerski P, Waters J, Margrie TW, Helmchen F, Denk W, Brecht M, Osten P. Lentivirus-based genetic manipulations of cortical neurons and their optical and electrophysiological monitoring in vivo. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 18206-18211. PMID: 15608064, PMCID: PMC539748, DOI: 10.1073/pnas.0407976101.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 2Calcium-Calmodulin-Dependent Protein KinasesElectrophysiologyGenetic VectorsGreen Fluorescent ProteinsHippocampusImage Processing, Computer-AssistedLentivirusMiceMice, Inbred C57BLMicroscopyNeuronsPhenotypePhotonsPromoter Regions, GeneticRecombinant ProteinsRNA, Small InterferingRNA, Small NuclearSynapsinsConceptsU6 promoter-driven expressionMicroscopy-based techniquesGenetic manipulationGene deliveryLentiviral vectorsGene functionGene knockdownSubsequent phenotypic analysisPromoter-driven expressionCellular response propertiesSmall networksTwo-photon microscopyTwo-photon time-lapse imagingCortical neuronsEfficient meansMicroscopyAlpha-calcium/calmodulin-dependent protein kinase IIThe transcription factor orthodenticle homeobox 2 influences axonal projections and vulnerability of midbrain dopaminergic neurons
Chung CY, Licznerski P, Alavian KN, Simeone A, Lin Z, Martin E, Vance J, Isacson O. The transcription factor orthodenticle homeobox 2 influences axonal projections and vulnerability of midbrain dopaminergic neurons. Brain 2010, 133: 2022-2031. PMID: 20573704, PMCID: PMC2892944, DOI: 10.1093/brain/awq142.Peer-Reviewed Original ResearchConceptsMidbrain dopaminergic neuronsVentral mesencephalic culturesTranscription factor orthodenticle homeobox 2Orthodenticle homeobox 2Dopaminergic neuronsMesencephalic culturesShort hairpin RNAHomeobox 2A10 dopaminergic neuronsCyclase-activating peptideHairpin RNAConditional knockout miceVentral mesencephalonNeuronal vulnerabilityDopaminergic projectionsAxonal projectionsParkinson's diseaseAdult miceKnockout miceMN9D cellsNeuropilin-2Elevated geneNeuronsNeuropilin-1Human midbrainA negative regulator of MAP kinase causes depressive behavior
Duric V, Banasr M, Licznerski P, Schmidt HD, Stockmeier CA, Simen AA, Newton SS, Duman RS. A negative regulator of MAP kinase causes depressive behavior. Nature Medicine 2010, 16: 1328-1332. PMID: 20953200, PMCID: PMC3066515, DOI: 10.1038/nm.2219.Peer-Reviewed Original Research