The role of mitochondrial dehydrogenases in the generation of oxidative stress

► Respiratory complexes may not be the only major sites of ROS formation in mitochondria. ► E3 subunit of α-ketoglutarate dehydrogenase generates superoxide and hydrogen peroxide. ► Disease-causing mutations of the E3 subunit have increased ROS-generating capability. ► α-Glycerophosphate dehydrogenase is a unique ROS-generating site in mitochondria. ► ROS production by α-glycerophosphate dehydrogenase is stimulated by Ca2+ even in damaged mitochondria.