2022
Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas
Zhang H, Li B, Huang Q, López-Giráldez F, Tanaka Y, Lin Q, Mehta S, Wang G, Graham M, Liu X, Park I, Eichmann A, Min W, Zhou J. Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas. Nature Communications 2022, 13: 7637. PMID: 36496409, PMCID: PMC9741628, DOI: 10.1038/s41467-022-35262-w.Peer-Reviewed Original ResearchConceptsMitochondrial dysfunctionThioredoxin 2Single-cell RNA-seq analysisRNA-seq analysisMutant miceNuclear genesMitochondrial proteinsMitochondrial localizationHuman retinal diseasesTranscriptional factorsGene expressionMutant retinasMitochondrial activityExtracellular matrixNovel mechanismVascular maturationArteriovenous malformationsGenetic deficiencyVessel growthSmad2Mouse retinaVascular malformationsMechanistic studiesBasement membraneRetinal vascular malformationsBrown adipose TRX2 deficiency activates mtDNA-NLRP3 to impair thermogenesis and protect against diet-induced insulin resistance
Huang Y, Zhou JH, Zhang H, Canfrán-Duque A, Singh AK, Perry RJ, Shulman G, Fernandez-Hernando C, Min W. Brown adipose TRX2 deficiency activates mtDNA-NLRP3 to impair thermogenesis and protect against diet-induced insulin resistance. Journal Of Clinical Investigation 2022, 132 PMID: 35202005, PMCID: PMC9057632, DOI: 10.1172/jci148852.Peer-Reviewed Original ResearchConceptsBrown adipose tissueBAT inflammationInsulin resistanceMitochondrial reactive oxygen speciesReactive oxygen speciesAberrant innate immune responsesDiet-induced insulin resistanceSystematic metabolismDiet-induced obesityNLRP3 inflammasome pathwayWhole-body energy metabolismCGAS/STINGInnate immune responseFatty acid oxidationExcessive mitochondrial reactive oxygen speciesMetabolic benefitsImmune responseInflammasome pathwayAdipose tissueInflammationInhibition reversesLipid uptakeLipid metabolismThioredoxin 2Adaptive thermogenesis
2019
A Unique SUMO-Interacting Motif of Trx2 Is Critical for Its Mitochondrial Presequence Processing and Anti-oxidant Activity
Chen C, Wang K, Zhang H, Zhou HJ, Chen Y, Min W. A Unique SUMO-Interacting Motif of Trx2 Is Critical for Its Mitochondrial Presequence Processing and Anti-oxidant Activity. Frontiers In Physiology 2019, 10: 1089. PMID: 31555141, PMCID: PMC6727865, DOI: 10.3389/fphys.2019.01089.Peer-Reviewed Original ResearchSUMO-interacting motifMitochondrial processing peptidaseReactive oxygen speciesMitochondrial intermediate peptidaseStress-induced cellular senescenceOxidative stress-induced cellular senescenceMitochondrial redox proteinsMitochondrial thioredoxin 2Excess reactive oxygen speciesMitochondrial processingPresequence processingProcessing peptidaseTrx2 proteinMitochondrial targetingMassive reactive oxygen speciesAntisenescence activityCellular senescenceThioredoxin 2Chemical inhibitionMature formRedox proteinsUnprocessed formProteinTrx2Catalytic site
2015
Thioredoxin-2 Inhibits Mitochondrial Reactive Oxygen Species Generation and Apoptosis Stress Kinase-1 Activity to Maintain Cardiac Function
Huang Q, Zhou HJ, Zhang H, Huang Y, Hinojosa-Kirschenbaum F, Fan P, Yao L, Belardinelli L, Tellides G, Giordano FJ, Budas GR, Min W. Thioredoxin-2 Inhibits Mitochondrial Reactive Oxygen Species Generation and Apoptosis Stress Kinase-1 Activity to Maintain Cardiac Function. Circulation 2015, 131: 1082-1097. PMID: 25628390, PMCID: PMC4374031, DOI: 10.1161/circulationaha.114.012725.Peer-Reviewed Original ResearchConceptsMitochondrial reactive oxygen species generationReactive oxygen species generationOxygen species generationASK1-dependent apoptosisMitochondrial reactive oxygen species productionPhosphorylation/activityKey mitochondrial proteinsSpecies generationMitochondrial membrane depolarizationKinase 1 activityMitochondrial proteinsReactive oxygen species productionCellular redoxMitochondrial Trx2Inhibition of ASK1Apoptotic signalingOxygen species productionThioredoxin 2Protein expression levelsKinase 1ATP productionASK1 inhibitionKnockout miceMitochondrial ultrastructureASK1 inhibitors
2010
Chapter 19 Thioredoxin and Redox Signaling in Vasculature—Studies Using Trx2 Endothelium-Specific Transgenic Mice
Min W, Xu L, Zhou H, Huang Q, Zhang H, He Y, Zhe X, Luo Y. Chapter 19 Thioredoxin and Redox Signaling in Vasculature—Studies Using Trx2 Endothelium-Specific Transgenic Mice. Methods In Enzymology 2010, 474: 315-324. PMID: 20609919, DOI: 10.1016/s0076-6879(10)74019-2.Peer-Reviewed Original ResearchConceptsReactive oxygen speciesCellular reactive oxygen speciesMitochondrial antioxidant systemVivo functional assaysTRX2 geneRedox signalingTransgenic miceRedox genesThioredoxin 2Functional analysisHuman diseasesFunctional assaysAntioxidant systemOxygen speciesGenesCritical roleEndothelial cell culturesCell culturesPrimary lineTrx2TransgenesisThioredoxinMitochondriaSignalingSpecies