Inhibition of STING-induced mitochondrial Drp1/N-GSDMD-mediated MtDNA release alleviates Sepsis-induced lung injury.
Uncover the STING-Drp1-N-GSDMD axis that drives mitochondrial dysfunction and lung injury in sepsis. Targeting this pathway could lead to novel therapies to prevent and treat acute respiratory distress syndrome.
This study investigates the mechanistic role of the STING pathway in sepsis-induced lung injury. Using clinical ARDS models and animal models of acute lung injury, the researchers found that STING mediates a positive feedback loop with the pyroptosis pathway, leading to mitochondrial dysfunction and inflammatory responses. Specifically, STING regulates the interaction between Drp1 and N-GSDMD on the mitochondrial membrane, linking mitochondrial fission to pyroptosis. Genetically or pharmacologically targeting this STING-mediated mitochondrial homeostasis pathway could offer a promising therapeutic approach for sepsis-induced acute lung injury. The findings provide important insights into the complex interplay between inflammation and cell death pathways in the context of respiratory distress.