STINGing organelle surface with acid.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) innate immune pathway has emerged as a critical driver of inflammation in a variety of settings, such as virus infection, cellular stress, tissue damage, and aging. The pathway detects microbial and host-derived double-stranded DNA (dsDNA) in the cytosol and triggers the production of type I interferons and proinflammatory cytokines that help eliminate the invading pathogens. STING is a mobile protein. After its binding to cyclic GMP-AMP, which is generated by cGAS in the presence of cytosolic dsDNA, STING exits the ER, translocates to the Golgi and then to recycling endosomes (REs), finally reaching lysosomes. In the course of its travel, STING recruits TBK1 from the cytosol and triggers type I interferon and proinflammatory responses through the activation of IRF3 and NF-κB at the trans-Golgi network (TGN).