DNASE1L3 surveils mitochondrial DNA on the surface of distinct mammalian cells.

ABSTRACT: The extracellular space is a critical environment for discriminating self versus non-self nucleic acids and initiating the appropriate immune responses through signaling cascades to relay information about extracellular nucleic acids. Here, we provide evidence that oxidized mitochondrial DNA is tethered to the surface of select mammalian cells through cell surface proteins and heparan sulfate proteoglycans. We demonstrate that cell surface DNA accumulates in large clusters that partially overlap with domains enriched in RNA binding proteins. Finally, we show that human and murine B cell surfaces contain DNA that can be cleared by the secreted nuclease DNASE1L3, and that patients with a DNASE1L3 missense variant associated with increased risk for autoimmune disease harbor increased l

SUBMITTER: Porat J 

PROVIDER: S-EPMC12632612 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature