The malate shuttle detoxifies ammonia in exhausted T cells by producing 2-ketoglutarate

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 …