Lysosomal movements during heterophagy and autophagy: with special reference to nematolysosome and wrapping lysosome

Recent studies on lysosomal movements during heterophagy and autophagy performed in our laboratory for the past several years were reviewed; methods for the investigation of lysosomes and the cytoskeleton in these studies mainly involved electron microscopic cytochemistry. Lysosomal movements during heterophagy were observed in cultured rat alveolar macrophages taking up horseradish peroxidase (HRP) and rat peroxidase-antiperoxidase (PAP) by fluid-phase pinocytosis and adsorptive pinocytosis, respectively. A characteristic lysosomal change which was induced by the pinocytosis was the appearance of long, threadlike lysosomes (nematolysosomes) in the cytoplasm. The effects of actin filament destabilizer and antimicrotubular drug on lysosomal changes revealed that the appearance of nematolysosomes was dependent on the presence of both actin filaments and microtubules. The close morphological relationship between lysosomes and cytoskeletal elements, such as actin filaments and microtubules in the alveolar macrophages, supports the participation of the cytoskeletal system in the regulatory mechanism of lysosomal movements. In the study of the lysosomal wrapping mechanism (LWM), which is one type of lysosomal movement that occurs during autophagy, it was found that the occurrence of LWM was dependent on energy--namely, the supply of ATP--and on the presence of actin filaments. However, deconstruction of microtubules induced or favored the occurrence of LWM. It is conceivable that the LWM is also related to the cytoskeletal system. We conclude that intracellular dynamics of lysosomes during heterophagy and autophagy are largely a consequence of complicated modulation by the cytoskeletal system.