Freeze-fracturing studies of mitochondrial myopathy. A correlated clinical, biochemical and morphological investigation.

Freeze-fracture studies of pathologically changed mitochondria in situ from muscle biopsies of a 9.5-year-old girl with a mitochondrial myopathy were correlated with clinical, biochemical and histochemical investigations. In the ultrathin sections giant mitochondria with densely packed cristae membranes - often reoriented to concentric circles - and, in addition, paracrystalline mitochondrial inclusions were found. The freeze fracture faces of such transformed mitochondria and preparations of their inner and outer membranes provided a morphological insight in the macromolecular structure of the mitochondrial membrane under such pathological conditions. The results lead to the hypothesis that part of the transformed mitochondria stay active functionally for an extended period by maintaining the delimitation from the cytoplasm and by preserving the macromolecular membrane architecture. This hypothesis could explain the slow progression of the myogenic symptoms.