Fig. 1: Ammonia-induced T-cell death.
From: Ammonia death: a novel potential strategy to augment immunotherapy in cancer
In mitochondrial glutamine metabolism, ammonia (NH3) is produced and subsequently leaves the mitochondria to enter the lysosomes, where it reacts with H+ to form NH4 +. This process results in elevated lysosomal pH, thereby impairing lysosomal function. The excessive accumulation of NH3 in the cytoplasm inhibits its normal transport into lysosomes, leading to a reverse flow into the mitochondria, which causes mitochondrial damage. Damaged mitochondria are usually degraded through autophagy; however, an increased lysosomal pH hinders lysosomal enzymatic activity, which obstructs the removal of dysfunctional mitochondria. Damaged mitochondria accumulation subsequently induces effector T-cell death. Created with BioRender.com.
