Fig. 5.

PSACH chondrocyte death results from intense cellular stress. Schematic showing that MT-COMP intracellular ER retention stimulates ER stress through CHOP-mediated UPR generating an inflammatory response. Prolonged ER stress also produces excessive ROS (reactive oxygen species) causing oxidative stress that further contributes to the inflammatory process and creates a self-perpetuating stress loop in chondrocytes. This results in the death of growth plate chondrocytes, which translates into diminished long-bone growth and skeletal dysplasia.