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

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© 2020 The Authors. Published under the terms of the CC BY 4.0 license

This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Mitochondrial DNA (mtDNA) can trigger various pro‐inflammatory signalling pathways by endosomal localised TLR9 or via cytosolic cGAS‐STING or via cytosolic inflammasome (AIM2 or NLRP3). Top: TLR9 binds mtDNA in the endosome eliciting an NF‐κB‐dependent pro‐inflammatory signalling program. Middle: cGAS recognises mtDNA in the cytosol and activates endoplasmic reticulum (ER)‐localised STING triggering an interferon response. Bottom: mtDNA‐dependent inflammasome activity leads to caspase‐1‐dependent maturation or pro‐inflammatory IL‐1 and IL‐8.