Taken together, these data suggest that the excess of mitochondrial ROS, resulting from impaired lysosome-mediated autophagic degradation of damaged mitochondria, triggers Gα12/Src-mediated phosphorylation of ZO-1, which disrupts tight junction integrity and activates ZONAB signaling, causing epithelial dysfunction in cystinosis cells. Here, SRC is linked to cystinosis.