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| 001 | 284615 | ||
| 005 | 20240229155053.0 | ||
| 024 | 7 | _ | |a 10.1038/s41590-023-01636-5 |2 doi |
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| 100 | 1 | _ | |a Weisshaar, Nina |0 P:(DE-He78)4e185694e1e726dc738bad0a0c41cdd0 |b 0 |e First author |
| 245 | _ | _ | |a The malate shuttle detoxifies ammonia in exhausted T cells by producing 2-ketoglutarate. |
| 260 | _ | _ | |a London |c 2023 |b Springer Nature Limited |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1700485108_7064 |2 PUB:(DE-HGF) |
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| 500 | _ | _ | |a 2023 Nov;24(11):1921-1932 / #EA:D192#LA:D192# / HI-TRON |
| 520 | _ | _ | |a The malate shuttle is traditionally understood to maintain NAD+/NADH balance between the cytosol and mitochondria. Whether the malate shuttle has additional functions is unclear. Here we show that chronic viral infections induce CD8+ T cell expression of GOT1, a central enzyme in the malate shuttle. Got1 deficiency decreased the NAD+/NADH ratio and limited antiviral CD8+ T cell responses to chronic infection; however, increasing the NAD+/NADH ratio did not restore T cell responses. Got1 deficiency reduced the production of the ammonia scavenger 2-ketoglutarate (2-KG) from glutaminolysis and led to a toxic accumulation of ammonia in CD8+ T cells. Supplementation with 2-KG assimilated and detoxified ammonia in Got1-deficient T cells and restored antiviral responses. These data indicate that the major function of the malate shuttle in CD8+ T cells is not to maintain the NAD+/NADH balance but rather to detoxify ammonia and enable sustainable ammonia-neutral glutamine catabolism in CD8+ T cells during chronic infection. |
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| 700 | 1 | _ | |a Ma, Sicong |b 1 |
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| 700 | 1 | _ | |a Buettner, Michael |b 10 |
| 700 | 1 | _ | |a Poschet, Gernot |b 11 |
| 700 | 1 | _ | |a Klinke, Glynis |b 12 |
| 700 | 1 | _ | |a Schulz, Michael |b 13 |
| 700 | 1 | _ | |a Kunze-Rohrbach, Nina |b 14 |
| 700 | 1 | _ | |a Kerber, Carolin |b 15 |
| 700 | 1 | _ | |a Klein, Isabel Madeleine |b 16 |
| 700 | 1 | _ | |a Wu, Jingxia |b 17 |
| 700 | 1 | _ | |a Wang, Xi |b 18 |
| 700 | 1 | _ | |a Cui, Guoliang |0 P:(DE-He78)0b7ce76033a6756b91f5bfb12602e20b |b 19 |e Last author |u dkfz |
| 773 | _ | _ | |a 10.1038/s41590-023-01636-5 |0 PERI:(DE-600)2026412-4 |n 11 |p 1921-1932 |t Nature immunology |v 24 |y 2023 |x 1529-2908 |
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