Interestingly, a connection between apoptosis and increased ROS production has been suggested to play an important role in the pathophysiology of mitochondrial diseases associated with COX deficiency.29,30 We showed that the expression of wild-type APOPT1 in mutant fibroblast cells led to an increase in the amount of COX and a reduction of ROS production to normal levels. The gene discussed is COA8; the disease is hyperinsulinemic hypoglycemia, familial, 4.