Mitochondrial calcium content and oxidative phosphorylation in heart and skeletal muscle of dystrophic mice.

Mitochondrial calcium overloading was investigated in the genetically dystrophic mouse (strains 129/ReJ dy/dy) as a possible contributing factor to the development of muscle fiber necrosis. Mitochondrial calcium concentrations were significantly elevated in both skeletal muscle and heart organelles. Because mitochondria were isolated in the presence of ruthenium red this finding was not the result of an artefact of isolation. State 3 respiration rates and concomitantly the respiratory control ratios were slightly decreased in skeletal muscle, but not in heart mitochondria. This abnormality could result from calcium overloading in a small fraction of the mitochondria. Fractionation of skeletal muscle mitochondria on sucrose gradients gave two distinct populations of dystrophic organelles, one with high calcium, whereas normal skeletal muscle mitochondria and heart organelles showed only one broad band on the gradient. The results support the idea that both skeletal muscle and heart are affected in dystrophic mice, strain 129/ReJ dy/dy and also that in the dystrophic mouse the process of cell necrosis is associated with cellular calcium overloading.