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• W4387451548 abstract "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." @default.
• W4387451548 created "2023-10-10" @default.
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• W4387451548 date "2023-10-09" @default.
• W4387451548 modified "2023-10-11" @default.
• W4387451548 title "The malate shuttle detoxifies ammonia in exhausted T cells by producing 2-ketoglutarate" @default.
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• W4387451548 doi "https://doi.org/10.1038/s41590-023-01636-5" @default.
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• W4387451548 hasPublicationYear "2023" @default.
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