2025
Polyamine metabolism is dysregulated in COXFA4-related mitochondrial disease
Marquez J, Viviano S, Beckman E, Thies J, Friedland-Little J, Lam C, Deniz E, Shelkowitz E. Polyamine metabolism is dysregulated in COXFA4-related mitochondrial disease. Human Genetics And Genomics Advances 2025, 6: 100418. PMID: 39967265, PMCID: PMC11946867, DOI: 10.1016/j.xhgg.2025.100418.Peer-Reviewed Original ResearchOrnithine decarboxylase pathwayCytochrome c oxidaseMitochondrial diseaseCause of mitochondrial diseaseAnalysis of cellular gene expressionSubunits of cytochrome c oxidaseC oxidaseTissue-specific diseasesCellular gene expressionDeficiency of cytochrome c oxidaseLeigh-like diseaseElectron donor NADHDownstream deficienciesMitochondrial membraneProtein complexesCellular functionsOxidative phosphorylationProtein subunitsGene expressionMetabolic pathwaysPolyamine metabolismPathwayProteinPoor growthAdenosine triphosphate
2024
Molecular Profiling of Mouse Models of Loss or Gain of Function of the KCNT1 (Slack) Potassium Channel and Antisense Oligonucleotide Treatment
Sun F, Wang H, Wu J, Quraishi I, Zhang Y, Pedram M, Gao B, Jonas E, Nguyen V, Wu S, Mabrouk O, Jafar-nejad P, Kaczmarek L. Molecular Profiling of Mouse Models of Loss or Gain of Function of the KCNT1 (Slack) Potassium Channel and Antisense Oligonucleotide Treatment. Biomolecules 2024, 14: 1397. PMID: 39595574, PMCID: PMC11591899, DOI: 10.3390/biom14111397.Peer-Reviewed Original ResearchWild-type miceKO miceSpectrum of epilepsy syndromesAntisense oligonucleotidesGain-of-function variantsAntisense oligonucleotide treatmentEpileptic phenotypePotassium channelsKCNT1Molecular profilingOligonucleotide treatmentAnimal modelsEpilepsy syndromesC-terminal mutationsIncreased expressionCerebral cortexMiceExpression of multiple proteinsComprehensive proteomic analysisDisease modelsCortical mitochondriaMolecular differencesDensity of mitochondrial cristaeMitochondrial membraneTreatmentOrganization of a functional glycolytic metabolon on mitochondria for metabolic efficiency
Wang H, Vant J, Zhang A, Sanchez R, Wu Y, Micou M, Luczak V, Whiddon Z, Carlson N, Yu S, Jabbo M, Yoon S, Abushawish A, Ghassemian M, Masubuchi T, Gan Q, Watanabe S, Griffis E, Hammarlund M, Singharoy A, Pekkurnaz G. Organization of a functional glycolytic metabolon on mitochondria for metabolic efficiency. Nature Metabolism 2024, 6: 1712-1735. PMID: 39261628, DOI: 10.1038/s42255-024-01121-9.Peer-Reviewed Original ResearchConceptsO-GlcNAc transferaseO-GlcNAcylation sitesGlycolytic metabolonO-GlcNAcylationEnzyme O-GlcNAc transferaseOuter mitochondrial membraneDynamic O-GlcNAcylationPost-translational modificationsReduced ATP generationMitochondrial ATP productionMetabolic efficiencyEnergy-demanding tissuesCellular energy sourceOGT activityMitochondrial associationRegulatory domainMitochondrial membraneMultiple cell typesATP generationATP productionMitochondrial functionMitochondrial couplingMetabolonCell typesGlucose flux
2023
Sfxn5 Regulation of Actin Polymerization for Neutrophil Spreading Depends on a Citrate-Cholesterol-PI(4,5)P2 Pathway.
Zhang H, Meng L, Liu Y, Jiang J, He Z, Qin J, Wang C, Yang M, He K, Yang J, Chen K, He Q, Tang W, Fan S, Ren C. Sfxn5 Regulation of Actin Polymerization for Neutrophil Spreading Depends on a Citrate-Cholesterol-PI(4,5)P2 Pathway. The Journal Of Immunology 2023, 211: 462-473. PMID: 37326485, DOI: 10.4049/jimmunol.2200863.Peer-Reviewed Original ResearchConceptsRegulation of actin polymerizationActin polymerizationNeutrophil spreadingCell spreadingLevels of phosphatidylinositol 4,5-bisphosphatePromote actin polymerizationNeutrophil actin polymerizationPhysiological cellular functionsPhosphatidylinositol 4,5-bisphosphateCytosolic citrateSmall interfering RNA transfectionFamily proteinsSFXN5Acetyl-CoAPI(4,5)P2 levelsMitochondrial membraneSpreading neutrophilsMetabolite transportCellular functionsMorpholino injectionCellular phenotypesCitrate transporterPlasma membraneDownstream metabolic productsDecreased neutrophil recruitmentIdentity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions
Bernardi P, Gerle C, Halestrap A, Jonas E, Karch J, Mnatsakanyan N, Pavlov E, Sheu S, Soukas A. Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions. Cell Death & Differentiation 2023, 30: 1869-1885. PMID: 37460667, PMCID: PMC10406888, DOI: 10.1038/s41418-023-01187-0.Peer-Reviewed Original ResearchConceptsMitochondrial permeability transition poreMitochondrial permeability transitionAdenine nucleotide translocasePermeability transition poreATP synthase dimersTransition poreInner mitochondrial membrane permeabilityC subunit ringOuter mitochondrial membraneMitochondrial membrane permeabilityDeath of cellsMPTP openingNecrotic cell deathMitochondrial membraneNucleotide translocaseTransient mPTP openingMitochondrial bioenergeticsSub-conductance statesMolecular identityPermeability transitionCell deathPhysiological roleNon-selective channelsDiscovery decadesMembrane permeabilityMitochondrial DNA and the STING pathway are required for hepatic stellate cell activation
Arumugam S, Li B, Boodapati S, Nathanson M, Sun B, Ouyang X, Mehal W. Mitochondrial DNA and the STING pathway are required for hepatic stellate cell activation. Hepatology 2023, 78: 1448-1461. PMID: 37013923, PMCID: PMC10804318, DOI: 10.1097/hep.0000000000000388.Peer-Reviewed Original ResearchConceptsVoltage-dependent anion channelBioenergetic capacityMitochondrial DNATranscriptional upregulationCyclic GMP-AMP synthaseGMP-AMP synthaseTranscriptional regulationBioenergetic organellesFunctional mitochondriaMitochondrial membraneExternal mitochondrial membraneAnabolic pathwaysMitochondrial massAnion channelInterferon genesHSC transdifferentiationSubsequent activationCGAS-STINGTransdifferentiationIRF3 pathwayPathwaySTING pathwayGenesMitochondriaQuiescent HSCs
2022
Overexpression of UCP3 decreases mitochondrial efficiency in mouse skeletal muscle in vivo
Codella R, Alves TC, Befroy DE, Choi CS, Luzi L, Rothman DL, Kibbey RG, Shulman GI. Overexpression of UCP3 decreases mitochondrial efficiency in mouse skeletal muscle in vivo. FEBS Letters 2022, 597: 309-319. PMID: 36114012, DOI: 10.1002/1873-3468.14494.Peer-Reviewed Original ResearchConceptsOverexpression of UCP3ATP synthesisMitochondrial oxidationMitochondrial transmembrane proteinInner mitochondrial membraneSkeletal muscleMitochondrial oxidative phosphorylationMitochondrial oxidative metabolismMuscle-specific overexpressionMouse skeletal muscleTransmembrane proteinMitochondrial membraneProton leakPrecise functionOxidative phosphorylationMitochondrial efficiencyUCP3 expressionMitochondrial inefficiencyOverexpressionProtein 3UCP3Oxidative metabolismVivoMagnetic resonance spectroscopyPhosphorylationCombinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS
Shi X, Reinstadler B, Shah H, To TL, Byrne K, Summer L, Calvo SE, Goldberger O, Doench JG, Mootha VK, Shen H. Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS. Nature Communications 2022, 13: 2483. PMID: 35513392, PMCID: PMC9072411, DOI: 10.1038/s41467-022-30126-9.Peer-Reviewed Original ResearchConceptsDe novo purine biosynthesisMitochondrial iron uptakeStructure-guided mutagenesisNovo purine biosynthesisMetabolic stateMitochondrial glutathione transportGlutathione importGenetic interactionsGenetic perturbationsDifferent metabolic environmentsFitness defectsLack of substrateGene interactionsMitochondrial OXPHOSMitochondrial membranePurine biosynthesisCarrier familyTransport assaysKO cellsIron uptakeGlutathione transportTransport activityIron homeostasisGlutathione homeostasisGenes
2021
The loss of DHX15 impairs endothelial energy metabolism, lymphatic drainage and tumor metastasis in mice
Ribera J, Portolés I, Córdoba-Jover B, Rodríguez-Vita J, Casals G, González-de la Presa B, Graupera M, Solsona-Vilarrasa E, Garcia-Ruiz C, Fernández-Checa JC, Soria G, Tudela R, Esteve-Codina A, Espadas G, Sabidó E, Jiménez W, Sessa WC, Morales-Ruiz M. The loss of DHX15 impairs endothelial energy metabolism, lymphatic drainage and tumor metastasis in mice. Communications Biology 2021, 4: 1192. PMID: 34654883, PMCID: PMC8519955, DOI: 10.1038/s42003-021-02722-w.Peer-Reviewed Original ResearchConceptsKey cellular processesIntracellular ATP productionCellular processesZebrafish embryosDownstream substratesATP biosynthesisProteome analysisMitochondrial membraneEndothelial cellsDHX15ATP productionRegulatory functionsDifferential expressionComplex IVascular regulatory functionEnergy metabolismVascular biologyTumor metastasisTherapeutical targetGene deficiencyPrimary tumor growthLower oxygen consumptionVascular physiologyDownregulation of VEGFCells
2020
Identification of miPEP133 as a novel tumor-suppressor microprotein encoded by miR-34a pri-miRNA
Kang M, Tang B, Li J, Zhou Z, Liu K, Wang R, Jiang Z, Bi F, Patrick D, Kim D, Mitra AK, Yang-Hartwich Y. Identification of miPEP133 as a novel tumor-suppressor microprotein encoded by miR-34a pri-miRNA. Molecular Cancer 2020, 19: 143. PMID: 32928232, PMCID: PMC7489042, DOI: 10.1186/s12943-020-01248-9.Peer-Reviewed Original ResearchConceptsNon-coding RNA transcriptsNasopharyngeal carcinomaCancer cell linesP53 transcriptional activationPrognostic markerTumor suppressor functionAmino acid residuesCell linesTumor growthNovel microproteinWild-type p53Cellular functionsMetastatic nasopharyngeal carcinomaTranscriptional activationPotential prognostic markerMitochondrial membraneUnfavorable prognostic markerCervical cancer cell linesRNA transcriptsMitochondrial massTumor suppressorMiR-34a expressionAcid residuesNormal human colonNPC clinical samplesOxidative stress battles neuronal Bcl-xL in a fight to the death
Park HA, Broman K, Jonas EA. Oxidative stress battles neuronal Bcl-xL in a fight to the death. Neural Regeneration Research 2020, 16: 12-15. PMID: 32788441, PMCID: PMC7818872, DOI: 10.4103/1673-5374.286946.Peer-Reviewed Original ResearchBcl-xLMitochondrial membraneBcl-xL.BCL2 proteinFO ATP synthaseBcl-XL bindsPost-translational phosphorylationOxidative stressBcl-x geneSynaptic vesicle recyclingActivation of caspasesPro-survival proteinsMitochondrial ATP productionAnti-apoptotic roleUndergoes proteolytic cleavageMultiprotein complexesATP synthaseTranscription factorsVesicle recyclingBCL2 familyApoptotic signalingKey regulatorPhysiological processesAlters formationATP productionRETREG1/FAM134B mediated autophagosomal degradation of AMFR/GP78 and OPA1 —a dual organellar turnover mechanism
Mookherjee D, Das S, Mukherjee R, Bera M, Jana S, Chakrabarti S, Chakrabarti O. RETREG1/FAM134B mediated autophagosomal degradation of AMFR/GP78 and OPA1 —a dual organellar turnover mechanism. Autophagy 2020, 17: 1729-1752. PMID: 32559118, PMCID: PMC8354597, DOI: 10.1080/15548627.2020.1783118.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutophagosomesCell Line, TumorChlorocebus aethiopsCOS CellsGene Knockdown TechniquesGTP PhosphohydrolasesHeLa CellsHumansIntracellular Signaling Peptides and ProteinsLysosomesMembrane ProteinsMicroscopy, ConfocalMicroscopy, Electron, TransmissionReal-Time Polymerase Chain ReactionReceptors, Autocrine Motility FactorConceptsInner mitochondrial membraneRETREG1/FAM134BEndoplasmic reticulumMitochondrial membraneFluorescent proteinAutophagosomal degradationOuter mitochondrial membrane proteinMahogunin Ring Finger-1OPA1 mitochondrial dynaminMicrotubule associated protein 1 light chain 3Outer mitochondrial membrane 20AMFR/gp78Cellular surveillance systemsMitochondrial membrane proteinInteresting new geneAutocrine motility factor receptorOuter mitochondrial membraneLC3-interacting regionMAP1LC3/LC3Protein 1 light chain 3Blue fluorescent proteinSQSTM1/p62Green fluorescent proteinRed fluorescent proteinReticulophagy regulator 1In-vivo Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient Uncoupler
Alpert N, Pelletier-Galarneau M, Kim S, Petibon Y, Sun T, Ramos-Torres K, Normandin M, Fakhri G. In-vivo Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient Uncoupler. Frontiers In Physiology 2020, 11: 491. PMID: 32499721, PMCID: PMC7243673, DOI: 10.3389/fphys.2020.00491.Peer-Reviewed Original ResearchMitochondrial membrane potentialPositron emission tomographyProton gradient uncouplerMembrane potentialIntracoronary infusionEmission tomographyPositron emission tomography scanBolus plus infusionVolume of distributionMitochondrial membraneCellular membrane potentialBAM15InfusionPreliminary dose-response experimentsMaximum depolarizationDose-response experimentsIn vivo imagingSecular equilibrium
2019
Involvement of hemoglobins in the pathophysiology of Alzheimer's disease
Altinoz M, Guloksuz S, Schmidt-Kastner R, Kenis G, Ince B, Rutten B. Involvement of hemoglobins in the pathophysiology of Alzheimer's disease. Experimental Gerontology 2019, 126: 110680. PMID: 31382012, DOI: 10.1016/j.exger.2019.110680.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseNeurodegenerative disordersPathogenesis of ADCourse of ADNitric oxideIncreased Hb levelsTangle-bearing neuronsInner mitochondrial membraneBlood-brain barrierAD brain samplesLevels of HbCentral nervous systemHeme-containing proteinsRole of HbFunction of intracellularMultiple beneficial effectsHb transcriptionHb levelsAD brainImmunohistochemical studyMitochondrial membranePossible candidate moleculesBiological processesCellular respirationNervous systemVitamin E Prevents ΔN-Bcl-xL-associate Mitochondrial Dysfunction in Primary Hippocampal Neurons (P14-024-19)
Park H, Mnatsakanyan N, Broman K, Jonas E. Vitamin E Prevents ΔN-Bcl-xL-associate Mitochondrial Dysfunction in Primary Hippocampal Neurons (P14-024-19). Current Developments In Nutrition 2019, 3: nzz052.p14-024-19. PMCID: PMC6574370, DOI: 10.1093/cdn/nzz052.p14-024-19.Peer-Reviewed Original ResearchBcl-xL.Bcl-xLPrimary hippocampal neuronsMitochondrial dysfunctionRedox statusBcl-xL protein levelsCaspase-dependent cleavageAnti-apoptotic Bcl-xLMitochondrial redox statusPro-survival proteinsNeuronal deathMitochondrial oxidative stressHippocampal neuronsOxidative stressReactive oxygen species formationMitochondrial membraneCaspase activitySubsequent oxidative stressMitochondrial potentialMitochondrial functionNeuronal energy metabolismOxygen species formationDependent cleavageOxidative stress productionEnergy metabolism
2018
The Mitochondrial Translocator Protein and the Emerging Link Between Oxidative Stress and Arrhythmias in the Diabetic Heart
Ilkan Z, Akar FG. The Mitochondrial Translocator Protein and the Emerging Link Between Oxidative Stress and Arrhythmias in the Diabetic Heart. Frontiers In Physiology 2018, 9: 1518. PMID: 30416455, PMCID: PMC6212558, DOI: 10.3389/fphys.2018.01518.Peer-Reviewed Original Research
2017
Inhibition of Bcl-xL prevents pro-death actions of ΔN-Bcl-xL at the mitochondrial inner membrane during glutamate excitotoxicity
Park HA, Licznerski P, Mnatsakanyan N, Niu Y, Sacchetti S, Wu J, Polster BM, Alavian KN, Jonas EA. Inhibition of Bcl-xL prevents pro-death actions of ΔN-Bcl-xL at the mitochondrial inner membrane during glutamate excitotoxicity. Cell Death & Differentiation 2017, 24: 1963-1974. PMID: 28777375, PMCID: PMC5635221, DOI: 10.1038/cdd.2017.123.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsbcl-X ProteinBiphenyl CompoundsCell DeathCyclosporineGlutamic AcidMembrane Potential, MitochondrialMitochondrial MembranesMitochondrial Proton-Translocating ATPasesModels, BiologicalMutant ProteinsNeuritesNeurotoxinsNitrophenolsPiperazinesProtein SubunitsRats, Sprague-DawleyRhodaminesSulfonamidesConceptsBcl-xLABT-737ΔN-BclMitochondrial membraneWEHI-539ATP synthase c-subunitMitochondrial inner membrane depolarizationPro-death actionInner membrane depolarizationMitochondrial inner membraneOuter mitochondrial membraneMitochondrial inner membrane potentialATP synthase activityActivation of BaxInner membrane potentialMitochondrial permeability transition poreMitochondrial membrane potentialMembrane potentialPermeability transition poreAnti-apoptotic activityC subunitInner membraneB-cell lymphoma extra-large proteinBax activationGlutamate toxicityThe Mitochondrial Permeability Transition Pore: Molecular Structure and Function in Health and Disease
Jonas E, Porter G, Beutner G, Mnatsakanyan N, Park H, Mehta N, Chen R, Alavian K. The Mitochondrial Permeability Transition Pore: Molecular Structure and Function in Health and Disease. Biological And Medical Physics, Biomedical Engineering 2017, 69-105. DOI: 10.1007/978-3-319-55539-3_3.Peer-Reviewed Original ResearchMitochondrial permeability transition porePermeability transition poreCell deathTransition poreMitochondrial inner membraneInner mitochondrial membraneC subunitATP synthaseInner membraneOuter membraneMitochondrial membraneCardiac developmentRegulatory mechanismsOxidative phosphorylationATP productionMitochondrial functionMolecular componentsMitochondrial efficiencyOsmotic dysregulationCell functionLarge conductanceRecent findingsPersistent openingMembraneIon transportStructural features and lipid binding domain of tubulin on biomimetic mitochondrial membranes
Hoogerheide D, Noskov S, Jacobs D, Bergdoll L, Silin V, Worcester D, Abramson J, Nanda H, Rostovtseva T, Bezrukov S. Structural features and lipid binding domain of tubulin on biomimetic mitochondrial membranes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e3622-e3631. PMID: 28420794, PMCID: PMC5422764, DOI: 10.1073/pnas.1619806114.Peer-Reviewed Original ResearchConceptsMitochondrial outer membraneMitochondrial membraneOuter membraneDimeric tubulinPeripheral membrane proteinsMembrane-binding domainOuter mitochondrial membraneDomain of tubulinIntegral proteinsMembrane proteinsCytosolic proteinsPhysiological roleHelix H10TubulinLipid headgroupsProteinComplex mechanismsMembranePeripheral bindingStructural featuresEssential stepCytoskeletonElectrochemical impedance spectroscopyMitochondriaDomain
2016
Human Atg8-cardiolipin interactions in mitophagy: Specific properties of LC3B, GABARAPL2 and GABARAP
Antón Z, Landajuela A, Hervás JH, Montes LR, Hernández-Tiedra S, Velasco G, Goñi FM, Alonso A. Human Atg8-cardiolipin interactions in mitophagy: Specific properties of LC3B, GABARAPL2 and GABARAP. Autophagy 2016, 12: 2386-2403. PMID: 27764541, PMCID: PMC5172498, DOI: 10.1080/15548627.2016.1240856.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SequenceApoptosis Regulatory ProteinsAutophagyAutophagy-Related Protein 8 FamilyCardiolipinsCell Line, TumorCell MembraneDronabinolGlioblastomaHumansHydrophobic and Hydrophilic InteractionsMicrotubule-Associated ProteinsMitochondriaMitochondrial MembranesMitophagyPressureProtein BindingRotenoneSaccharomyces cerevisiae ProteinsSequence Homology, Amino AcidConceptsSelective mitochondrial autophagyOuter mitochondrial membraneHuman Atg8Quantitative biophysical techniquesHuman orthologAutophagosome formationMitochondrial autophagyMitochondrial membraneAutophagic processC-terminusGABARAPL2GABARAPPhospholipid cardiolipinBiophysical techniquesMitochondriaOrthologsMembrane fluidityCardiolipinLC3BMitophagyPositive cooperativitySpecific roleU87MG cellsAutophagyHydrophilic environment
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