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Heartbreakers: innate sensors ZBP1 and cGAS linked to cardiotoxicity

Wen Chen , Thirumala-Devi Kanneganti

Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN, USA
* Correspondence: Thirumala-Devi Kanneganti(Thirumala-Devi.Kanneganti@StJude.org)

As an innate immune sensor, ZBP1 senses infections and cellular damage, triggering the formation of a PANoptosome complex containing caspase-8 and RIPKs that activates the inflammasome, drives inflammatory cell death, and produces proinflammatory cytokines; however, ZBP1’s role in mitochondrial damage was not previously known. A recent publication in Cell by Lei et al. shows that ZBP1 senses mitochondrial genome instability and forms a complex with cGAS and RIPKs to sustain type I interferon signaling and drive cardiotoxicity.

https://doi.org/10.1038/s41422-023-00861-9

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