Abstract

Cytoplasmic mitochondrial DNA (mtDNA) can trigger the interferon response to promote disease progression, but mtDNA sensing mechanisms remain elusive. Lei et al. have shown that Z-DNA binding protein1 (ZBP1) cooperates with cyclic GMP-AMP synthase (cGAS) to sense Z-form mtDNA and transmit mtDNA stress signals to promote diseases such as cardiotoxicity, providing an important piece of the mtDNA stress landscape.

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