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 stressLipidDeletionA Th17 cell-intrinsic glutathione/mitochondrial-IL-22 axis protects against intestinal inflammation
Bonetti L, Horkova V, Grusdat M, Longworth J, Guerra L, Kurniawan H, Franchina D, Soriano-Baguet L, Binsfeld C, Verschueren C, Spath S, Ewen A, Koncina E, Gérardy J, Kobayashi T, Dostert C, Farinelle S, Härm J, Fan Y, Chen Y, Harris I, Lang P, Vasiliou V, Waisman A, Letellier E, Becher B, Mittelbronn M, Brenner D. A Th17 cell-intrinsic glutathione/mitochondrial-IL-22 axis protects against intestinal inflammation. Cell Metabolism 2024, 36: 1726-1744.e10. PMID: 38986617, DOI: 10.1016/j.cmet.2024.06.010.Peer-Reviewed Original ResearchReactive oxygen speciesMitochondrial functionCatalytic subunit of glutamate cysteine ligaseMitochondrial gene expressionDecreased cellular ATPPhosphorylation of 4E-BP1Disrupt mitochondrial functionReduced phosphorylation of 4E-BP1T cell-specific ablationCell's antioxidant mechanismsCell-specific ablationCatalytic subunitIL-22Cellular signalingIntestinal homeostasisIL-22 productionSignificant reactive oxygen speciesSubunit of glutamate cysteine ligaseGene expressionReduced IL-22 productionReduced phosphorylationCellular ATPGut protectionProtein synthesisGlutamate cysteine ligase