2024
Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression
Asantewaa G, Tuttle E, Ward N, Kang Y, Kim Y, Kavanagh M, Girnius N, Chen Y, Rodriguez K, Hecht F, Zocchi M, Smorodintsev-Schiller L, Scales T, Taylor K, Alimohammadi F, Duncan R, Sechrist Z, Agostini-Vulaj D, Schafer X, Chang H, Smith Z, O’Connor T, Whelan S, Selfors L, Crowdis J, Gray G, Bronson R, Brenner D, Rufini A, Dirksen R, Hezel A, Huber A, Munger J, Cravatt B, Vasiliou V, Cole C, DeNicola G, Harris I. Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression. Nature Communications 2024, 15: 6152. PMID: 39034312, PMCID: PMC11271484, DOI: 10.1038/s41467-024-50454-2.Peer-Reviewed Original ResearchConceptsGlutamate-cysteine ligase catalytic subunitLipid abundanceLipogenic enzyme expressionAbundance in vivoLipid productionCatalytic subunitRepress Nrf2Transcription factorsNrf2 repressionAdult tissuesSynthesis of GSHEnzyme expressionNon-redundantRedox bufferMouse liverLoss of GSHTriglyceride productionIn vivo modelsAbundanceGlutathione synthesisLiver balanceFat storesOxidative stressLipidDeletion
2022
Glutathione-dependent redox balance characterizes the distinct metabolic properties of follicular and marginal zone B cells
Franchina DG, Kurniawan H, Grusdat M, Binsfeld C, Guerra L, Bonetti L, Soriano-Baguet L, Ewen A, Kobayashi T, Farinelle S, Minafra AR, Vandamme N, Carpentier A, Borgmann FK, Jäger C, Chen Y, Kleinewietfeld M, Vasiliou V, Mittelbronn M, Hiller K, Lang PA, Brenner D. Glutathione-dependent redox balance characterizes the distinct metabolic properties of follicular and marginal zone B cells. Nature Communications 2022, 13: 1789. PMID: 35379825, PMCID: PMC8980022, DOI: 10.1038/s41467-022-29426-x.Peer-Reviewed Original ResearchConceptsElectron transport chainMarginal zone B cellsMitochondrial electron transport chainGlutamate-cysteine ligaseCatalytic subunitRedox controlCell-specific ablationRedox balanceTransport chainMetabolic dependenciesCysteine ligaseProtein synthesisMetabolite succinateMTOR activationGlutathione synthesisATP levelsMetabolic propertiesB cellsMetabolic principlesMetabolic featuresDistinct metabolic propertiesMZBCellsActivationLigase
2020
Glutathione Restricts Serine Metabolism to Preserve Regulatory T Cell Function
Kurniawan H, Franchina DG, Guerra L, Bonetti L, -Baguet LS, Grusdat M, Schlicker L, Hunewald O, Dostert C, Merz MP, Binsfeld C, Duncan GS, Farinelle S, Nonnenmacher Y, Haight J, Das Gupta D, Ewen A, Taskesen R, Halder R, Chen Y, Jäger C, Ollert M, Wilmes P, Vasiliou V, Harris IS, Knobbe-Thomsen CB, Turner JD, Mak TW, Lohoff M, Meiser J, Hiller K, Brenner D. Glutathione Restricts Serine Metabolism to Preserve Regulatory T Cell Function. Cell Metabolism 2020, 31: 920-936.e7. PMID: 32213345, PMCID: PMC7265172, DOI: 10.1016/j.cmet.2020.03.004.Peer-Reviewed Original ResearchConceptsSuppressive capacityRegulatory T cell functionTreg suppressive capacityTreg-specific ablationAnti-tumor responseT cell functionSerine metabolismTreg functionalityFoxp3 expressionPrevent autoimmunitySevere autoimmunityTreg differentiationImmune homeostasisEffector TGlutamate-cysteine ligaseCell responsesTregsMTOR activationMutant miceCell functionAutoimmunitySerine availabilityGlutathione synthesisCysteine ligaseMice