Figure 1.

STING stimulation by stressed organelles: an interactive triad. STING plays a critical role in preserving health but also mediates disease, even in the absence of infectious triggers. Mitochondrial DNA (red lines) has recently emerged as a trigger of STING activation. The endogenous ligand mediating the ER-STING reciprocal relationship is not clear. The endoplasmic reticulum (ER) and mitochondria share a very close anatomic and functional relationship, and together modulate homeostatic and pathologic levels of intracellular calcium (Ca²⁺) and reactive oxygen species (ROS). This relationship may generate the “missing ligand” for ER stress-mediated STING activation via mitochondrial DNA release.