Transfer: [Frontiers of Science and Technology] Wuhan University Song Zhiyin and other teams discover a new mechanism of mitochondrial DNA release

Mitochondria are highly dynamic double-membrane organelles that contain mitochondrial DNA (mtDNA), which encodes key subunits of the mitochondrial respiratory chain complex and is essential for ATP production

Unlike nuclear DNA, mtDNA lacks protective histones and is particularly vulnerable to mitochondrial damaging factors such as ROS

In response to various infections, cyclic GMP-AMP (cGAMP) synthase (cGAS) acts as a cytosolic DNA sensor that activates the linker STING by generating the second messenger cGAMP to activate the innate immune response

Cardiolipin is a unique dimeric phospholipid mainly present in the inner mitochondrial membrane to maintain the integrity of the mitochondrial membrane

Acetaminophen (APAP) is a potent antipyretic and analgesic, but APAP overdose is the most common drug poisoning and the leading cause of acute liver failure worldwide

Here, the study shows that Sam50 depletion or APAP treatment results in mtDNA release through the Bax/Bak mitochondrial pore, followed by activation of the cGAS-STING signaling pathway and liver inflammation in mice