2,4-dinitrophenol, lysosomal breakdown and rapid myofilament degradation in vertebrate skeletal muscle

1. The possibility that rapid Ca2+-uptake by skeletal muscle mitochondria may cause local reductions in pHi (by H+/Ca2+ exchange) and so promote lysosomal breakdown has been explored using amphibian and mammalian preparations. Recent studies suggested that such a sequence of events is possible in cardiac muscle. 2. However, extensive muscle damage can still be initiated in skeletal muscle when the mitochondria are uncoupled so that Ca2+-uptake is prevented. 3. DNP alone induces extensive myofilament degradation which is similar to that produced by A23187 and caffeine and described previously. 4. It is suggested that (a) the known action of DNP in promoting lysosomal labilization in living cells is produced by mitochondrial uncoupling and the release of stored Ca2+, (b) raised [Ca2+]i promotes lysosomal breakdown in skeletal muscle, so that the hydrolases released effect myofilament dissolution rapidly. 5. DNP also rapidly causes septation and division of the mitochondria in mammalian skeletal muscle.