Interference with lysosomal proteolysis fails to reduce cardiac myosin degradation

Chloroquine (a lysosomotropic agent) and leupeptin (an inhibitor of thiol proteinases including lysosomal cathepsins B, H, and L) reduced the rate of total protein degradation in cultured fetal mouse hearts by 25% (p < 0.01). Simultaneously, the rate of degradation of myosin was not diminished by either agent. In contrast, insulin reduced the rate of total protein degradation by 16% and of myosin degradation by 13% (p < 0.01 for both). These results indicate that primary interference with lysosomal proteolytic processes fails to inhibit myosin degradation; it is suggested that the degradation of myosin (and perhaps other myofibrillar proteins) is normally accomplished via nonlysosomal mechanisms.