Apoptosis and ROS detoxification enzymes correlate with cytochrome c oxidase deficiency in mitochondrial encephalomyopathies

The aim of this work was to investigate in muscle the role of apoptosis and of oxidative stress in mitochondrial disorders with dysfunction of respira tory chain. In patients with cytochrome c oxidase deficiency (COX) we found a variable number of myofibers with apoptotic nuclei that matched with the level of enzymatic reduction and roughly correlated with muscle weakness. In parallel, a positive immunostaining for apoptosis-related proteins and M n and Cu/Zn superoxide dismutase (SOD) were mostly localized in COX-negativ e fibers. Moreover, glutathione peroxidase activity was increased in muscle s with high number of SOD-positive myofibers and prominent apoptotic featur es. No signs of apoptosis were observed in patients with deficiencies of co mplexes I and II and without muscle weakness. These data suggest that apopt osis along with increased ROS production, revealed by anti-oxidant enzymes overexpression, may play an important role in the pathophysiology of mitoch ondrial diseases associated with COX deficiency.