[en] Cells rely on antioxidants to survive. The most abundant antioxidant is glutathione (GSH). The synthesis of GSH is non-redundantly controlled by the glutamate-cysteine ligase catalytic subunit (GCLC). GSH imbalance is implicated in many diseases, but the requirement for GSH in adult tissues is unclear. To interrogate this, we developed a series of in vivo models to induce Gclc deletion in adult animals. We find that GSH is essential to lipid abundance in vivo. GSH levels are reported to be highest in liver tissue, which is also a hub for lipid production. While the loss of GSH did not cause liver failure, it decreased lipogenic enzyme expression, circulating triglyceride levels, and fat stores. Mechanistically, we found that GSH promotes lipid abundance by repressing NRF2, a transcription factor induced by oxidative stress. These studies identify GSH as a fulcrum in the liver's balance of redox buffering and triglyceride production.
Disciplines :
Immunology & infectious disease
Author, co-author :
Asantewaa, Gloria; Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY, USA, 14642 ; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642 ; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642
Tuttle, Emily T; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642 ; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642
Ward, Nathan P; Department of Metabolism and Physiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA, 33612
Kang, Yun Pyo; Department of Metabolism and Physiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA, 33612
Kim, Yumi; Department of Metabolism and Physiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA, 33612
Kavanagh, Madeline E; Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA, 92037
Girnius, Nomeda; Department of Cell Biology, Harvard Medical School, Boston, MA, USA, 02115
Chen, Ying; Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA, 06520
Duncan, Renae; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642 ; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642
Rodriguez, Katherine; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642 ; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642
Hecht, Fabio; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642 ; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642
Zocchi, Marco; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642 ; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642
Smorodintsev-Schiller, Leonid; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642 ; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642
Scales, TashJaé Q; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642 ; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642
Taylor, Kira; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642 ; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642
Alimohammadi, Fatemeh; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642 ; Department of Pharmacology and Physiology, University of Rochester, Rochester, NY, USA, 14642
Sechrist, Zachary R; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642 ; Department of Surgery and Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA, 14642 ; Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA, 14642
Agostini-Vulaj, Diana; Department of Surgery and Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA, 14642
Schafer, Xenia L; Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY, USA, 14642 ; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642
Chang, Hayley; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642 ; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642
Smith, Zachary; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642 ; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642
O'Connor, Thomas N; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642 ; Department of Surgery and Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA, 14642
Whelan, Sarah; Leicester Cancer Research Centre, University of Leicester, Leicester, LE2 7LX, UK
Selfors, Laura M; Department of Cell Biology, Harvard Medical School, Boston, MA, USA, 02115
Crowdis, Jett; Department of Cell Biology, Harvard Medical School, Boston, MA, USA, 02115
Gray, G Kenneth; Department of Cell Biology, Harvard Medical School, Boston, MA, USA, 02115
Bronson, Roderick T; Department of Cell Biology, Harvard Medical School, Boston, MA, USA, 02115
BRENNER, Dirk ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Immunology and Genetics ; Experimental & Molecular Immunology, Department of Infection and Immunity, Luxembourg Institute of Health, 29 Rue Henri Koch, Esch-sur-Alzette, Luxembourg ; Odense Research Center for Anaphylaxis (ORCA), Department of Dermatology and Allergy Center, Odense University Hospital, University of Southern Denmark, Odense, Denmark
Rufini, Alessandro; Leicester Cancer Research Centre, University of Leicester, Leicester, LE2 7LX, UK ; Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, 20133, Milan, Italy
Dirksen, Robert T; Department of Pharmacology and Physiology, University of Rochester, Rochester, NY, USA, 14642
Hezel, Aram F; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642 ; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642
Huber, Aaron R; Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA, 14642
Munger, Josh; Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY, USA, 14642 ; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642
Cravatt, Benjamin F; Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA, 92037
Vasiliou, Vasilis; Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA, 06520
Cole, Calvin L; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642 ; Department of Surgery and Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA, 14642
DeNicola, Gina M; Department of Metabolism and Physiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA, 33612
Harris, Isaac S; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA, 14642 ; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA, 14642
