The ubiquitin-proteasome pathway in distal myopathy with rimmed vacuoles.

The protein synthesis and degradation of eukaryotic cells must be highly selective and tightly regulated to maintain cellular homeostasis. Like other tissues, muscle contains multiple pathways for protein breakdown including the lysosomal, Ca2+-dependent, and cytosolic ATP-dependent and independent proteolytic systems. These pathways are considered to play important roles not only in cellular degeneration and death but also in cellular differentiation, growth and regeneration. In fact, many lysosomes appear in the regenerating skeletal muscle fibers (1), and they disappear as the myofibers mature. Distal myopathy with rimmed vacuole formation (DMRV) is a sporadic or an autosomal recessively inherited disorder characterized by the formation of rimmed vacuoles in skeletal muscle fibers. A rimmed vacuole is believed to be an autophagic vacuole in which activation of lysosomal proteases such as cathepsins B, L, or H have been reported (2, 3). Although the lysosomal system is not well developed in the differentiated mature myofiber, these cathepsins in DMRVare thought to derive from myofiber itself, not from macrophages. On the other hand, a calcium-dependent neutral proteinase has been suggested to be involved in the muscle degradation in Duchenne muscular dystrophy (DMD) (4, 5), in which