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

Mol Cell Neurosci. 2001 Apr;17(4):696-705. doi: 10.1006/mcne.2001.0970.


The aim of this work was to investigate in muscle the role of apoptosis and of oxidative stress in mitochondrial disorders with dysfunction of respiratory 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 Mn and Cu/Zn superoxide dismutase (SOD) were mostly localized in COX-negative fibers. Moreover, glutathione peroxidase activity was increased in muscles with high number of SOD-positive myofibers and prominent apoptotic features. No signs of apoptosis were observed in patients with deficiencies of complexes I and II and without muscle weakness. These data suggest that apoptosis along with increased ROS production, revealed by anti-oxidant enzymes overexpression, may play an important role in the pathophysiology of mitochondrial diseases associated with COX deficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apoptosis / physiology*
  • Biopsy
  • Caspase 1 / analysis
  • Caspase 3
  • Caspases / analysis
  • Child
  • Child, Preschool
  • Cytochrome-c Oxidase Deficiency*
  • DNA Fragmentation
  • Electron Transport Complex IV / analysis
  • Female
  • Glutathione Peroxidase / metabolism
  • Humans
  • In Situ Nick-End Labeling
  • Infant
  • Infant, Newborn
  • Male
  • Microscopy, Electron
  • Middle Aged
  • Mitochondrial Encephalomyopathies / enzymology*
  • Mitochondrial Encephalomyopathies / pathology*
  • Muscle Fibers, Skeletal / enzymology
  • Muscle Fibers, Skeletal / pathology
  • Muscle Fibers, Skeletal / ultrastructure
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / pathology
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / analysis
  • fas Receptor / analysis


  • Reactive Oxygen Species
  • fas Receptor
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Electron Transport Complex IV
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Caspase 1