Muscle fiber degradation in distal myopathy with rimmed vacuoles.

Late-onset distal myopathy showed numerous rimmed vacuoles with the same properties as autophagic vacuoles. Electron microscopy showed numerous degenerated mitochondria, glycogen, or cell membranes in rimmed vacuoles, but no evidence that these vacuoles engulfed and contained intact or partially disrupted myofibrils. Immunostaining for myosin, alpha-actinin, and actin, however, was sometimes positive within the vacuoles. Compared to the control muscle, there was increased staining activity by calpain around the rimmed vacuoles or in the cytoplasm of mainly atrophic fibers. The result seems to indicate an increase of calpain activity in these muscle fibers. We hypothesize that the myofibrils as well as mitochondria, glycogen, or cell membranes in this myopathy are degraded finally through a lysosomal autophagic process. However, the breakdown of the myofibrils may be not initiated by lysosomal activation; rather it may be the result of extralysosomal processes such as the calpain system.