| First Author | Eriksson S | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 6479 | PubMed ID | 25790857 |
| Mgi Jnum | J:221873 | Mgi Id | MGI:5641785 |
| Doi | 10.1038/ncomms7479 | Citation | Eriksson S, et al. (2015) Dietary methionine can sustain cytosolic redox homeostasis in the mouse liver. Nat Commun 6:6479 |
| abstractText | Across phyla, reduced nicotinamide adenine dinucleotide phosphate (NADPH) transfers intracellular reducing power to thioredoxin reductase-1 (TrxR1) and glutathione reductase (GR), thereby supporting fundamental housekeeping and antioxidant pathways. Here we show that a third, NADPH-independent pathway can bypass the need for TrxR1 and GR in mammalian liver. Most mice genetically engineered to lack both TrxR1 and GR in all hepatocytes ('TR/GR-null livers') remain long-term viable. TR/GR-null livers cannot reduce oxidized glutathione disulfide using NADPH but still require continuous glutathione synthesis. Inhibition of cystathionine gamma-lyase causes rapid necrosis of TR/GR-null livers, indicating that methionine-fueled trans-sulfuration supplies the necessary cysteine precursor for glutathione synthesis via an NADPH-independent pathway. We further show that dietary methionine provides the cytosolic disulfide-reducing power and all sulfur amino acids in TR/GR-null livers. Although NADPH is generally considered an essential reducing currency, these results indicate that hepatocytes can adequately sustain cytosolic redox homeostasis pathways using either NADPH or methionine. |
