| Abstract: | Mechanisms of autophagic proteolysis in the liver have been studied using vinblastine. Vinblastine stimulated degradation by induced autophagy in a dose-related fashion 1, 2]. Insulin partially inhibits the increased rate of degradation and the formation of autophagosomes as well as the lysosomal fragility induced by vinblastine. Insulin has little effect, however, on basal, non-induced degradation rates. Vinblastine-induced autophagy enhances the degradation of both ‘old’ and ‘newly’ synthesized proteins and is therefore in that sense a random process. The administration of high doses of colchicine also augments proteolysis. This effect is attributed to increase in autophagy. The very nascent vinblastine-induced autophagosomes appear to lack hydrolytic enzymes and acquire them only after fusion with lysosomes. The autophagolysosomal population induced by vinblastine is heterogeneous with respect to shape, size, content and density. Isolated secondary lysosomes (‘residual bodies’) lacking morphologically recognizable sequestered membranes (degradable substrate) show no release of degradation products. Autophagosomes fuse with secretory vesicles originating from the Golgi apparatus. |
