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We show that CATs in the basal metazoan phyla Cnidaria and Porifera are evolutionarily distinct from the rest of the metazoan CATs, including those of the phylum Placozoa that sit within an otherwise bilaterian invertebrate clade (Fig

The resulting glutamine surplus aggravates glutamine-induced osmotic stress in the cytoplasm, at the same time rendering more glutamine available for (i) its Slc7a6-mediated exchange for extracellular arginine, which increases intra-astrocytic accumulation of reactive nitrogen species (ii) glutamine transport to astrocytic mitochondria, which leads to mitochondrial dysfunction (the Trojan Horse mode of action)