Leaked Mitochondrial C1QBP Inhibits Activation of the DNA Sensor cGAS.

ABSTRACT: Cytosolic DNA from pathogens activates the DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) that produces the second messenger, cGAMP. cGAMP triggers a signal cascade leading to type I IFN expression. Host DNA is normally restricted in the cellular compartments of the nucleus and mitochondria. Recent studies have shown that DNA virus infection triggers mitochondrial stress, leading to the release of mitochondrial DNA to the cytosol and activation of cGAS; however, the regulatory mechanism of mitochondrial DNA-mediated cGAS activation is not well elucidated. In this study, we analyzed cGAS protein interactome in mouse RAW264.7 macrophages and found that cGAS interacted with C1QBP. C1QBP predominantly localized in the mitochondria and leaked into the cytosol during DNA virus infection. The

SUBMITTER: Song K 

PROVIDER: S-EPMC8492507 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature