2020
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 leakMaturationMetabolism
2019
The mitochondrial metabolic function of DJ‐1 is modulated by 14‐3‐3β
Weinert M, Millet A, Jonas EA, Alavian KN. The mitochondrial metabolic function of DJ‐1 is modulated by 14‐3‐3β. The FASEB Journal 2019, 33: 8925-8934. PMID: 31034784, PMCID: PMC6988861, DOI: 10.1096/fj.201802754r.Peer-Reviewed Original ResearchConceptsMitochondrial metabolic efficiencyMitochondrial metabolic functionDisease genesMetabolic efficiencyMetabolic functionsMajor signaling pathwaysNovel molecular mechanismHypoxia-dependent mannerParkinson's disease genesKey adaptive mechanismsMitochondrial plasticityChaperone activityCellular metabolic demandsMetabolic plasticityReactive oxygen speciesMolecular mechanismsOxidative phosphorylationPleiotropic functionsSignaling pathwaysDJ-1Cell survivalCancer cellsOxygen speciesAdaptive mechanismsPathophysiological conditions
2014
An uncoupling channel within the c-subunit ring of the F1FO ATP synthase is the mitochondrial permeability transition pore
Alavian KN, Beutner G, Lazrove E, Sacchetti S, Park HA, Licznerski P, Li H, Nabili P, Hockensmith K, Graham M, Porter GA, Jonas EA. An uncoupling channel within the c-subunit ring of the F1FO ATP synthase is the mitochondrial permeability transition pore. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 10580-10585. PMID: 24979777, PMCID: PMC4115574, DOI: 10.1073/pnas.1401591111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCell DeathHEK293 CellsHumansIon Channel GatingIon ChannelsLiposomesMitochondriaMitochondrial Membrane Transport ProteinsMitochondrial MembranesMitochondrial Permeability Transition PoreMutationProtein ConformationProtein SubunitsProton-Translocating ATPasesRatsReactive Oxygen SpeciesConceptsMitochondrial PT poreF1Fo-ATP synthaseATP synthasePermeability transitionCell deathCellular metabolic efficiencyInner mitochondrial membrane permeabilityOxygen species-induced cell deathC subunit ringATP synthase F1Mitochondrial membrane permeabilityMitochondrial permeability transitionC subunitPT poreTight regulationATP productionMolecular identitySingle-channel conductanceChannel closureLeak channelsMPTP openingMetabolic efficiencyMembrane permeabilityHealthy cellsOsmotic shifts
2013
PINK1 protects against cell death induced by mitochondrial depolarization, by phosphorylating Bcl-xL and impairing its pro-apoptotic cleavage
Arena G, Gelmetti V, Torosantucci L, Vignone D, Lamorte G, De Rosa P, Cilia E, Jonas EA, Valente EM. PINK1 protects against cell death induced by mitochondrial depolarization, by phosphorylating Bcl-xL and impairing its pro-apoptotic cleavage. Cell Death & Differentiation 2013, 20: 920-930. PMID: 23519076, PMCID: PMC3679455, DOI: 10.1038/cdd.2013.19.Peer-Reviewed Original ResearchConceptsBcl-xLMitochondrial depolarizationCell deathPro-autophagic protein Beclin-1Autosomal recessive Parkinson's diseaseBeclin-1Recessive Parkinson's diseaseAnti-apoptotic proteinsXL interactionMitochondrial kinaseProtein Beclin 1Mitochondrial traffickingMitochondrial homeostasisMitophagy pathwayBcl-xL.PINK1Functional linkCell survivalPathogenesis of PDNovel mechanismPINK1 genePathwayCleavageMitophagyParkinson's disease
2012
NAD kinase regulates the size of the NADPH pool and insulin secretion in pancreatic β-cells
Gray JP, Alavian KN, Jonas EA, Heart EA. NAD kinase regulates the size of the NADPH pool and insulin secretion in pancreatic β-cells. AJP Endocrinology And Metabolism 2012, 303: e191-e199. PMID: 22550069, PMCID: PMC3431206, DOI: 10.1152/ajpendo.00465.2011.Peer-Reviewed Original ResearchConceptsGlucose-stimulated insulin secretionInsulin secretionΒ-cellsPancreatic β-cellsRedox cycling agent menadioneRat β-cell lineΒ-cell lineINS-1 832/13 cellsTwo- to threefold increaseAntioxidant defense systemRodent isletsSecretionGlucose concentrationOxidative damageOxidative defenseThreefold increaseNADPH/Cytosolic reductasesAgent menadione