Figure 2.

General control nonderepressible-2 kinase (GCN2)-mediated amino acid sensing in the control of inflammation during cellular stress. Amino acid deficiency leads to accumulation of uncharged tRNAs, which are recognized by the nutrient sensor GCN2. Upon its activation, the phospho-GCN2 inhibits the translation initiation ternary complex through the phosphorylation of eIF2α, thus stalls the protein translation. As a result, the RNA-binding proteins are recruited to the translationally stalled mRNAs, forming stress granules that either arrest or decay the stalled mRNAs, and ultimately decreasing the inflammation. At the same time eIF2 phosphorylation leads to translation of specific mRNA, such as ATF4, which translates stress-response genes, GADD34, CHOP, etc. On the other hand, GCN2 pathway induces autophagy which reduces inflammation through inhibition of the reactive oxygen species and inflammasome activation.