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

Abstract

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.

Microautophagy in mammalian cells: Revisiting a 40-year-old conundrum

“…Several studies highlight a range of findings including: (1) that lysosomes show microautophagy activity in vitro, which may be a mechanism for degradation of soluble cytoplasmic constituents in vivo, 51 (2) a lysosomal wrapping mechanism having features resembling those of microautophagy, 6,52 (3) changes in microautophagy apparently related to intrinsic alterations within cells (e.g., liver protein content, rates of protein synthesis and degradation, volumes of lysosomal-vacuolar components), 53 and (4) characterization of starvation-induced microautophagic vacuoles. 54 Glaumann and colleagues 51 showed that isolated rat liver lysosomes incubated with Percoll particles in vitro contain a number of vesicles, some of which contain (one or more) Percoll particles plus surrounding fluid.…”

“…6,52 The LWM was reported to occur in a variety of tissues under various (and notably mostly nonphysiological) conditions as follows: (1) the uptake and translocation of horseradish peroxidase in mouse histiocytes, which are component cells of the mononuclear phagocytic system, 6 (2) isolated hepatocytes after administration of glucagon or of cyclic AMP, 6 (3) Yoshida ascites cells treated with cortisone acetate in vitro or in vivo, 6 (4) splenic macrophages isolated from γ-ray-irradiated rats, 6 (5) mouse histiocytes after ovalbumin administration. 6 The common characteristics of LWM described in the above studies were as follows: (1) ATP is consumed as energy source for both sequestration of a particular cytoplasmic cargo and its subsequent degradation, (2) control of LWM is apparently mediated by actin filaments rather than by microtubules and (3) protein synthesis is necessary for LWM. 6,52 Using electron microscopy as the main detection technique, several forms of microautophagy-like sequestration structures have been described in mouse/rat liver hepatocytes.…”

“…6 The common characteristics of LWM described in the above studies were as follows: (1) ATP is consumed as energy source for both sequestration of a particular cytoplasmic cargo and its subsequent degradation, (2) control of LWM is apparently mediated by actin filaments rather than by microtubules and (3) protein synthesis is necessary for LWM. 6,52 Using electron microscopy as the main detection technique, several forms of microautophagy-like sequestration structures have been described in mouse/rat liver hepatocytes. [53][54][55][56] How these structures are formed, however, has not been elucidated.…”

“…In subsequent investigations spanning some 30 years, other research groups have used the term microautophagy to describe lysosomal uptake but without providing much, if any, mechanistic insight into the process observed. [2][3][4][5][6][7] It is thus unclear whether these investigators were describing the same process at a mechanistic level.…”

A Three-dimensional Observation of Acid Phosphatase-positive Structures in Rat Testis by High Voltage Electron Microscopy

“…On the other hand, the findings also indicate that the phagocytosis and intracellular processing of phagosomes in Sertoli cells could be stimulated by heating the testis, which had been reported causing injury of germ cells12), because an increasing of the number of lysosomes, particularly secondary lysosomes were observed in the cytoplasm. The fact that the nematolysosome was absent in the testicular cells indicates that nematolysosomes are not a ubiquitous structure of all the types of cells and tissues, although they have been found in several kinds of cells1-4, [10][11][13][14][16][17][18][19][20][21][22]. Meanwhile, in another study dealt with luteal cells (our unpublished data), the nematolysosomes were found to be increased in number after luteal cells naturally go to regressing.…”