Mitochondrial myopathies are a clinical condition characterized by
muscle weakness and
fatigue in which the primary defect is localized at the level of the mitochondria. Microscopic examination shows accumulations of mitochondria at the fibre periphery (ragged red fibres) and in some cases mitochondrial paracrystalline inclusions. The spectrum of different
mitochondrial defects so far described is reviewed and data from cases investigated in this laboratory are described. The first case was a 17-year-old boy with a multisystem disorder whose muscle mitochondria showed low respiratory activity with all substrates, which doubled in the presence of uncoupler. Further investigation showed that the mitochondrial
ATPase activity was only 6% of normal. The next cases were a mother and daughter who showed a typical
lipid storage myopathy. The latter was treated successfully with oral
carnitine but the
myopathy persisted. Mitochondrial investigations indicated a low respiratory activity with
NAD-linked substrates but normal activity with
succinate and ascorbate + TMPD. A defect in the
NADH-CoQ reductase section of the respiratory chain was pinpointed possibly at an
iron-sulphur centre. The fourth and fifth cases were two sisters who exhibited no
lipid storage myopathy but whose mitochondrial activity was low with
NAD-linked substrates but normal with
succinate. Again a defect in the
NADH-CoQ reductase (complex I) of the respiratory chain was determined. They were also investigated using 31P-NMR. It was found after exercise that their muscle
creatine phosphate levels took seven times longer to return to pre-exercise concentrations than control subjects. These results are discussed with respect to the synthesis of
mitochondrial proteins and the influence that both the mitochondrial and nuclear
DNA have on this process.