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. 2020 Sep 18;27(11):2989–3003. doi: 10.1038/s41418-020-00624-8

Fig. 2. Interplay between the cGAS–STING signaling pathway and apoptosis.

Fig. 2

During apoptosis signaling the proapoptotic proteins such as BAK/BAX cause mitochondrial membrane permeabilisation and release of cytochrome c and mitochondrial DNA. Mitochondrial DNA can trigger cGAS–STING–TBK1 pathway to drive IFN-mediated immune responses. Whereas cytosolic cytochrome c drives the assembly of the Apaf1-caspaspe-9 apoptosome that subsequently activate the initiator caspases (e.g. caspase-3 and caspase-7) to mediate apoptosis. Caspase-3 negatively regulates cGAS–STING pathway resulting in cleavage of IRF3 and STING. On the other hand, STING activation causes ER-stress that ultimately results in apoptosis by via BAK/BAX activation and cytochrome c release. Red arrows indicate negative regulation.