2024
Alveolar Type 2 Cells With Impaired Proteostasis Signal to Monocyte-derived Macrophages Via a MIF/DDT-CD74 Signaling Network to Promotes Pulmonary Fibrosis in IPF
Kim S, Nouws J, Cooley J, Ahangari F, Leng L, Elias J, Kaminski N, Lee P, Redente E, Kang M, Sun H, Herzog E, Bucala R, Prasse A, Sauler M. Alveolar Type 2 Cells With Impaired Proteostasis Signal to Monocyte-derived Macrophages Via a MIF/DDT-CD74 Signaling Network to Promotes Pulmonary Fibrosis in IPF. 2024, a3001-a3001. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a3001.Peer-Reviewed Original ResearchReduced Epithelial NUPR1 Negatively Impacts Mitochondrial Function and Metabolism, and Increases Susceptibility to Emphysema
Nouws J, Yang T, Santofimia-Castaño P, Iovanna J, Sauler M. Reduced Epithelial NUPR1 Negatively Impacts Mitochondrial Function and Metabolism, and Increases Susceptibility to Emphysema. 2024, a2620-a2620. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a2620.Peer-Reviewed Original ResearchAltered extracellular matrix dynamics is associated with insulin resistance in adolescent children with obesity
Slusher A, Nouws J, Tokoglu F, Vash‐Margita A, Matthews M, Fitch M, Shankaran M, Hellerstein M, Caprio S. Altered extracellular matrix dynamics is associated with insulin resistance in adolescent children with obesity. Obesity 2024, 32: 593-602. PMID: 38410080, PMCID: PMC11034857, DOI: 10.1002/oby.23974.Peer-Reviewed Original ResearchConceptsSubcutaneous adipose tissueLiver fat contentInsulin resistanceInsulin sensitivityEctopic storage of lipidOral glucose tolerance testGluteal subcutaneous adipose tissueExtracellular matrix dynamicsMagnetic resonance imaging scansAdipose tissueBody fat distribution patternsFibrogenesis in vivoAdipocyte turnoverAssociated with insulin resistanceGlucose tolerance testFat distribution patternsWhole-body IRAdipose tissue insulin signalingTissue insulin signalingTolerance testGluteal fatImaging scansPathophysiological pathwaysAssociated with ratioObesityStem cell migration drives lung repair in living mice
Chioccioli M, Liu S, Magruder S, Tata A, Borriello L, McDonough J, Konkimalla A, Kim S, Nouws J, Gonzalez D, Traub B, Ye X, Yang T, Entenberg D, Krishnaswamy S, Hendry C, Kaminski N, Tata P, Sauler M. Stem cell migration drives lung repair in living mice. Developmental Cell 2024, 59: 830-840.e4. PMID: 38377991, PMCID: PMC11003834, DOI: 10.1016/j.devcel.2024.02.003.Peer-Reviewed Original ResearchStem cell migrationCell migrationAlveolar type 2 cellsAlveolar unitsStem cell motilityAlveolar type 1 cellsStem cell activityCellular response to injuryResponse to injuryType 2 cellsMotile phenotypeType 1 cellsCell motilityLung repairImpaired regenerationGenetic depletionCell activationAT2Stem cellsTissue repairAT1Longitudinal imagingInjuryMotilityCellular resolution
2023
Alterations in Adipose Tissue Distribution, Cell Morphology, and Function Mark Primary Insulin Hypersecretion in Youth With Obesity
Tricò D, Chiriacò M, Nouws J, Vash-Margita A, Kursawe R, Tarabra E, Galderisi A, Natali A, Giannini C, Hellerstein M, Ferrannini E, Caprio S. Alterations in Adipose Tissue Distribution, Cell Morphology, and Function Mark Primary Insulin Hypersecretion in Youth With Obesity. Diabetes 2023, 73: 941-952. PMID: 37870826, PMCID: PMC11109779, DOI: 10.2337/db23-0450.Peer-Reviewed Original ResearchPrimary insulin hypersecretionΒ-cell glucose sensitivityAdipose tissue distributionInsulin hypersecretionInsulin resistanceGlucose toleranceUnfavorable metabolic phenotypeWorse glucose toleranceLeptin serum levelsAbnormal glucose toleranceTissue distributionExcessive insulin secretionHigher leptin levelsVisceral fat depotsNon-diabetic adolescentsEuglycemic hyperinsulinemic clampWhole-body adiposityAbdominal subcutaneous adipocytesBody weight gainGlucose sensitivityPrimary hypersecretionGlucose intoleranceSerum levelsLeptin levelsChronic hyperinsulinemia
2018
Ethnicity and Common Genetic Variants Modulate Nonalcoholic Fatty Liver Disease (NAFLD) Metabolic Phenotype in Obese Youth
TRICO D, CAPRIO S, UMANO G, GALDERISI A, MATA M, NOUWS J, PIERPONT B, KIM G, SANTORO N. Ethnicity and Common Genetic Variants Modulate Nonalcoholic Fatty Liver Disease (NAFLD) Metabolic Phenotype in Obese Youth. Diabetes 2018, 67 DOI: 10.2337/db18-313-or.Peer-Reviewed Original ResearchNonalcoholic fatty liver diseasePediatric nonalcoholic fatty liver diseaseType 2 diabetesInsulin resistanceObese adolescentsInsulin sensitivityPrevalence of NAFLDHigher C-peptide levelsOral glucose tolerance testAfrican AmericansC-peptide levelsHigh fasting glucoseFatty liver diseaseGlucose tolerance testLower insulin sensitivityMajor risk factorZ-score BMIHepatic fat contentStrongest predictorCommon gene variantsFasting GlucoseNAFLD developmentGlucose toleranceLiver diseaseTolerance test
2015
A Role of the Inflammasome in the Low Storage Capacity of the Abdominal Subcutaneous Adipose Tissue in Obese Adolescents
Kursawe R, Dixit VD, Scherer PE, Santoro N, Narayan D, Gordillo R, Giannini C, Lopez X, Pierpont B, Nouws J, Shulman GI, Caprio S. A Role of the Inflammasome in the Low Storage Capacity of the Abdominal Subcutaneous Adipose Tissue in Obese Adolescents. Diabetes 2015, 65: 610-618. PMID: 26718495, PMCID: PMC4764142, DOI: 10.2337/db15-1478.Peer-Reviewed Original ResearchMeSH KeywordsAbdomenAcetyl-CoA CarboxylaseAdipogenesisAdiponectinAdolescentCarrier ProteinsCaspase 1ChildDown-RegulationFatty Acid Synthase, Type IFemaleGene Expression ProfilingGlucose Transporter Type 4HumansInflammasomesInsulin ResistanceInterleukin-1betaIntra-Abdominal FatLeptinLipogenesisLipoprotein LipaseMacrophagesMagnetic Resonance ImagingMaleNLR Family, Pyrin Domain-Containing 3 ProteinObesityPPAR gammaSirtuin 1Sterol Regulatory Element Binding Protein 1Subcutaneous FatToll-Like Receptor 4ConceptsVisceral adipose tissueObese adolescentsInsulin resistanceTissue inflammationNLRP3 inflammasomeAdipose tissueInnate immune cell sensorsAbdominal subcutaneous adipose tissueAbdominal adipose depotsAbdominal fat partitioningAdipogenesis/lipogenesisAdipose tissue inflammationProinflammatory cytokines interleukinInfiltration of macrophagesExpression of CASP1Subcutaneous adipose tissueInflammation markersSAT biopsiesIL-18Macrophage infiltrationVisceral fatCytokines interleukinSAT ratioInsulin sensitivityAdipose depots
2013
ACAD9, a complex I assembly factor with a moonlighting function in fatty acid oxidation deficiencies
Nouws J, Brinke H, Nijtmans L, Houten S. ACAD9, a complex I assembly factor with a moonlighting function in fatty acid oxidation deficiencies. Human Molecular Genetics 2013, 23: 1311-1319. PMID: 24158852, DOI: 10.1093/hmg/ddt521.Peer-Reviewed Original ResearchMeSH KeywordsAcyl-CoA Dehydrogenase, Long-ChainAcyl-CoA DehydrogenasesCarnitineCatalysisCell LineCongenital Bone Marrow Failure SyndromesElectron Transport Complex IEnzyme ActivationFatty AcidsHumansLipid Metabolism, Inborn ErrorsMitochondriaMitochondrial DiseasesModels, MolecularMolecular WeightMuscular DiseasesMutationOxidation-ReductionOxidative PhosphorylationProtein ConformationConceptsAcyl-CoA dehydrogenase 9Complex IFatty acid oxidationEnzymatic activityLong-chain acyl-CoA dehydrogenaseAcid oxidationAcyl-CoA dehydrogenaseDuplication eventsAssembly intermediatesKnockdown experimentsFatty acid loadingOxidative phosphorylationFatty acid oxidation deficiencyMetabolic pathwaysComplete rescueDeficient fibroblastsMajor metabolic pathwaysEnzyme activityControl fibroblastsFibroblastsVLCAD deficiencyPhosphorylationMitochondriaKnockdownProteinA Patient with Complex I Deficiency Caused by a Novel ACAD9 Mutation Not Responding to Riboflavin Treatment
Nouws J, Wibrand F, van den Brand M, Venselaar H, Duno M, Lund A, Trautner S, Nijtmans L, Østergard E. A Patient with Complex I Deficiency Caused by a Novel ACAD9 Mutation Not Responding to Riboflavin Treatment. JIMD Reports 2013, 12: 37-45. PMID: 23996478, PMCID: PMC3897792, DOI: 10.1007/8904_2013_242.Peer-Reviewed Original ResearchComplex I deficiencyI deficiencyAge 7 weeksHigher lactate levelsSevere hypertrophic cardiomyopathyMonths of ageNew pathogenic mutationsI protein levelsPatient fibroblastsACAD9 mutationsComplex I protein levelsCardiogenic shockIntercurrent illnessRespiratory insufficiencyMuscle weaknessHypertrophic cardiomyopathyRiboflavin treatmentFrequent causeHomozygous missense mutationLactate levelsRiboflavin supplementationPatientsRespiratory chain activityPathogenic mutationsProtein levels3‐Methylglutaconic aciduria—lessons from 50 genes and 977 patients
Wortmann S, Kluijtmans L, Rodenburg R, Sass J, Nouws J, van Kaauwen E, Kleefstra T, Tranebjaerg L, de Vries M, Isohanni P, Walter K, Alkuraya F, Smuts I, Reinecke C, van der Westhuizen F, Thorburn D, Smeitink J, Morava E, Wevers R. 3‐Methylglutaconic aciduria—lessons from 50 genes and 977 patients. Journal Of Inherited Metabolic Disease 2013, 36: 913-921. PMID: 23355087, DOI: 10.1007/s10545-012-9579-6.Peer-Reviewed Original ResearchConceptsMetabolic disordersMitochondrial dysfunctionElevated urinary excretionRoutine metabolic screeningPatient cohortUrinary excretionPatientsMitochondrial DNA depletionMetabolic screeningHydratase deficiencyInborn errorsRelated pathologiesUrine samplesDisordersAciduriaDysfunctionDNA depletionLeucine degradationRespiratory chain complex deficienciesMitochondrial disordersCommon denominatorComplex deficiencySERAC1Consistent featureOPA3
2012
The Assembly of Human Complex I
Nouws J, Calvaruso M, Nijtmans L. The Assembly of Human Complex I. 2012, 193-217. DOI: 10.1007/978-94-007-4138-6_10.Peer-Reviewed Original ResearchComplex IHuman mitochondrial complex IComplex I assemblyHuman complex IMitochondrial complex IPrecise molecular mechanismsMitochondrial genomeSpecialized proteinsFunctional enzymeMolecular mechanismsChaperonesAssemblyEnzymeStepwise processDifferent stepsGenomeSubunitsProteinDifferent stagesMembraneComplicated process
2011
Assembly factors as a new class of disease genes for mitochondrial complex I deficiency: cause, pathology and treatment options
Nouws J, Nijtmans L, Smeitink J, Vogel R. Assembly factors as a new class of disease genes for mitochondrial complex I deficiency: cause, pathology and treatment options. Brain 2011, 135: 12-22. PMID: 22036961, DOI: 10.1093/brain/awr261.Peer-Reviewed Original ResearchConceptsComplex I deficiencyAssembly factorsDisease genesI deficiencySpecific assembly factorsGeneral molecular mechanismMitochondrial complex I deficiencyOxidative phosphorylation disordersDisease-causing mutationsSuch genesMolecular mechanismsComplex IGenesLarge diversityProgressive encephalomyopathyChaperonesDiversityMutationsEncephalomyopathyDeficiencyNew classNDUFB7 and NDUFA8 are located at the intermembrane surface of complex I
Szklarczyk R, Wanschers B, Nabuurs S, Nouws J, Nijtmans L, Huynen M. NDUFB7 and NDUFA8 are located at the intermembrane surface of complex I. FEBS Letters 2011, 585: 737-743. PMID: 21310150, DOI: 10.1016/j.febslet.2011.01.046.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBiological AssayCell FractionationCell LineCloning, MolecularDisulfidesElectron Transport Complex IElectrophoresis, Polyacrylamide GelEndopeptidase KHumansIron-Sulfur ProteinsMitochondrial MembranesModels, MolecularMolecular Sequence DataNADH DehydrogenaseNADH, NADPH OxidoreductasesOxidation-ReductionProtein Structure, SecondaryProtein Structure, TertiaryProtein SubunitsSequence AlignmentSurface PropertiesConceptsDisulfide bridgesLarge protein complexesIntra-molecular disulfide bridgesEukaryotic subunitsEvolutionary originSequence conservationProtein complexesMembrane domainsMost subunitsNDUFA8Oxidative phosphorylationComplex ISubunitsNDUFB7LocalizationComplexesPhosphorylationNDUFS5Crystal structureConservationDomain
2010
Acyl-CoA Dehydrogenase 9 Is Required for the Biogenesis of Oxidative Phosphorylation Complex I
Nouws J, Nijtmans L, Houten S, van den Brand M, Huynen M, Venselaar H, Hoefs S, Gloerich J, Kronick J, Hutchin T, Willems P, Rodenburg R, Wanders R, van den Heuvel L, Smeitink J, Vogel R. Acyl-CoA Dehydrogenase 9 Is Required for the Biogenesis of Oxidative Phosphorylation Complex I. Cell Metabolism 2010, 12: 283-294. PMID: 20816094, DOI: 10.1016/j.cmet.2010.08.002.Peer-Reviewed Original ResearchMeSH KeywordsAcyl-CoA Dehydrogenase, Long-ChainAcyl-CoA DehydrogenasesAdaptor Proteins, Signal TransducingAmino Acid SequenceAnimalsCells, CulturedElectron Transport Complex IFatty AcidsFemaleFibroblastsHumansInfantMaleMitochondriaModels, MolecularMolecular Sequence DataMutationNADH DehydrogenaseOxidation-ReductionOxidative PhosphorylationPhylogenyPregnancyProtein Structure, TertiaryRNA InterferenceSequence AnalysisSequence Analysis, DNAConceptsAcyl-CoA dehydrogenase 9Complex I deficiencyFatty acid oxidationComplex IOxidative phosphorylation complexes IAcyl-CoA dehydrogenase familyMitochondrial metabolic pathwaysI deficiencyLong-chain acyl-CoA dehydrogenaseAcid oxidationAcyl-CoA dehydrogenaseFactors NDUFAF1Vertebrate lineageDehydrogenase familyRelated metabolic enzymesLong-chain fatty acidsMetabolic enzymesOxidative phosphorylationLong-chain fatty acid oxidationMitochondrial beta oxidationMetabolic pathwaysACAD9 mutationsBeta oxidationFatty acidsNDUFAF1