Figure 6.

Scheme showing the activation of the STING pathway by cytosolic DNA and regulation by metformin. Cytosolic dsDNA is recognized by cGAS, which leads to the generation of cGAMP. cGAMP binds and activates STING, which then translocate from the ER to perinuclear sites. This translocation results in the recruitment and activation of TBK1 by autophosphorylation. The activation of TBK1 phosphorylates the transcription factor IRF3, which translocates to the nucleus to induce transcription of type I IFN genes. Metformin can suppress the phosphorylation of AKT and promotion the expression of STING, which then further leads to the up-regulation of phosphorylation of IRF3 and the generation of IFN-β.