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. 2020 Mar 23;21(4):e49799. doi: 10.15252/embr.201949799

Figure 2. mtDNA‐dependent activation of cGAS‐STING signalling.

Figure 2

Various mitochondrial stresses including bacterial or viral infection can lead to mtDNA release. Alternatively, activation of BAX and BAK leads to outer mitochondrial membrane permeabilisation (MOMP) and mtDNA release. Once cytoplasmic, mtDNA can bind the DNA sensing protein cGAS that catalyses the production of the secondary messenger 2′3′ cyclic GMP–AMP (2′3′cGAMP) from ATP and GTP. cGAMP binds the adaptor molecule STING on the ER leading to activation of TBK1 kinase. Active TBK1 phosphorylates the transcription factor IRF3 initiating a type I interferon response.