Mitochondrial DNA sensing by STING signaling participates in inflammation, cancer and beyond.

Recent studies have revealed the diverse pathophysiological functions of mitochondria beyond traditional energetic metabolism in cells. Mitochondria-released damage-associated molecular patterns, particularly mitochondrial deoxyribonucleic acid (mtDNA), play a central role in host immune defenses against foreign pathogens. Newly discovered cGAS-STING signaling is responsible for microbial DNA recognition, and potentially participates in mitochondrial DNA sensing. Inappropriate inflammatory signaling mediated by mtDNA is implicated in various human diseases, especially infectious/inflammatory disease and cancer. In addition, mtDNA horizontal transfer between tumor cells and surrounding somatic cells has been recently observed and been associated with tumorigenesis and cancer progression. In this review, we will summarize the molecular signaling of mtDNA recognition (especially STING signaling), and discuss the underlying mechanism by which mtDNA transfer triggers cancer progression in human. Besides, we will highlight the central role of mtDNA in host immunity, with particular emphasis on mtDNA-induced NETs (neutrophil extracellular traps) formation, apoptosis and autophagy.