• Journal of Microbiology and Biotechnology
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• v.19 no.11
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• pp.1364-1368
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• 2009

Lysosomes, as a cell organelle type, are safe biological control agents that may be possible replacements for chemical antimicrobial agents because they are simply isolated from egg white. In this study, it was found that the lysosomes isolated from egg white exhibited pH-dependent antimicrobial activity, with the optimal activity found at pH 6.0. The efficiency of lysosomes in inhibiting bacterial growth and activity was evaluated over a 12-h treatment period. Seven different microorganisms were used as bacterial strains, and the lysosomes showed a significant antimicrobial effect against all strains. In addition, the antimicrobial activity was maintained for 100 days, and there did not appear to be any resistance of E. coli to the lysosomal activity up to the eighth culture. However, the lysosomes did not affect the viability of mammalian cells, suggesting the biocompatibility of lysosomes. These highly effective lysosomes have a bright future in the application of novel antimicrobial sources as a cell organelle type.

• Journal of Microbiology and Biotechnology
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• v.27 no.2
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• pp.372-379
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• 2017

The transport of lysosomal enzymes into the lysosomes depends on the phosphorylation of their chains and the binding of the phosphorylated residues to mannose-6-phosphate receptors. The efficiency of separation depends more on the phosphodiesterases (PDEs) than on the activity of the phosphorylation of mannose residues and can be determined in vitro. PDEs play important roles in regulation of the activation of lysosomes. The expression of proteins was confirmed by western blotting. All PDE4 series protein expression was reduced in high concentrations of rolipram. As a result of observing the fluorescence intensity after rolipram treatment, the lysosomal enzyme was activated at low concentrations and suppressed at high concentrations. High concentrations of rolipram recovered the original function. Antimicrobial activity was not shown in either 10 or $100{\mu}M$ concentrations of rolipram in treated HeLa cells in vitro. However, the higher anticancer activity at lower rolipram concentration was shown in lysosomal enzyme treated with $10{\mu}M$ of rolipram. The anticancer activity was confirmed through cathepsin B and D assay. Tranfection allowed examination of the relationship between PDE4 and lysosomal activity in more detail. Protein expression was confirmed to be reduced. Fluorescence intensity showed decreased activity of lysosomes and ROS in cells transfected with the antisense sequences of PDE4 A, B, C, and D. PDE4A showed anticancer activity, whereas lysosome from cells transfected with the antisense sequences of PDE4 B, C, and D had decreased anticancer activity. These results showed the PDE4 A, B, C, and D are conjunctly related with lysosomal activity.

• Journal of Microbiology and Biotechnology
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• v.25 no.2
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• pp.234-237
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• 2015

In this study, we developed lysosome-alginate beads for application as an oral drug delivery system (ODDS). The beads harboring lysosomes, which have antimicrobial activity, and various concentrations of alginate were characterized and optimized. For application as an ODDS, pH-dependent lysosome-alginate beads were generated, and the level of lysosome release was investigated by using antimicrobial tests. At low pH, lysosomes were not released from the lysosome-alginate beads; however, at neutral pH, similar to the pH in the intestine, lysosome release was confirmed, as determined by a high antimicrobial activity. This study shows the potential of such an ODDS for the in vivo treatment of infection with pathogens.

• Molecules and Cells
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• v.41 no.1
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• pp.45-49
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• 2018

Autophagy is a lysosome-dependent degradation process that is essential for maintaining cellular homeostasis. In recent years, more studies have focused on the late stages of autophagy. Our group discovered and studied the terminal step of autophagy, namely autophagic lysosome reformation (ALR). ALR is the process that regenerates functional lysosomes from autolysosomes, thus maintaining lysosome homeostasis. ALR involves clathrin-mediated membrane budding from autolysosomes, elongation of membrane tubules along microtubules with the pulling force provided by the motor protein KIF5B, proto-lysosome scission by dynamin 2, and finally maturation of proto-lysosomes to functional lysosomes. In this review, we will summarize progress in unveiling the molecular mechanisms underlying ALR and its potential pathophysiological roles.

• Applied Microscopy
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• v.28 no.4
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• pp.551-561
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• 1998

The autometallographic method was used to demonstrate the localization of mercury deposits in spleen of mouse. The mercury deposits were identified with the light and electron mocroscope. Mice were treated with methylmercuric chloride in the drinking water (demineralized water) for 40 days. Control and mercury treated groups showed no significant differences in mean body weight and spleen weight per one mouse. Mercury grains were appeared in the germinal center of white pulp consist of a preponderancing lymphocytes, not in red pulp and capsule. At the ultrastructural level, mercury deposits were restricted to lysosomes of macrophage and lymphocyte. Specially, volume in lysosomes of the macrophage was increased. These results suggest that mercury localization in lysosomes is associated with the change of immune activity.

• Molecules and Cells
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• v.45 no.9
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• pp.649-659
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• 2022

A long-term energy nutritional imbalance fundamentally causes the development of obesity and associated fat accumulation. Lysosomes, as nutrient-sensing and lipophagy centers, critically control cellular lipid catabolism in response to nutrient deprivation. However, whether lysosome activity is directly involved in nutrient-induced fat accumulation remains unclear. In this study, worm fat accumulation was induced by 1 mM glucose or 0.02 mM palmitic acid supplementation. Along with the elevation of fat accumulation, lysosomal number and acidification were also increased, suggesting that lysosome activity might be correlated with nutrient-induced fat deposition in Caenorhabditis elegans. Furthermore, treatments with the lysosomal inhibitors chloroquine and leupeptin significantly reduced basal and nutrient-induced fat accumulation in C. elegans. The knockdown of hlh-30, which is a critical gene in lysosomal biogenesis, also resulted in worm fat loss. Finally, the mutation of aak-2, daf-15, and rsks-1 showed that mTORC1 (mechanistic target of rapamycin complex-1) signaling mediated the effects of lysosomes on basal and nutrient-induced fat accumulation in C. elegans. Overall, this study reveals the previously undescribed role of lysosomes in overnutrition sensing, suggesting a new strategy for controlling body fat accumulation.

• Journal of Life Science
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• v.31 no.5
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• pp.527-535
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• 2021

Lysosomes are organelles surrounded by membranes that contain acid hydrolases; they degrade proteins, macromolecules, and lipids. According to nutrient conditions, lysosomes act as signaling hubs that regulate intracellular signaling pathways and are involved in the homeostasis of cells. Therefore, the lysosomal dysfunction occurs in various diseases, such as lysosomal storage disease, neurodegenerative diseases, and cancers. Multiple forms of stress can increase lysosomal membrane permeabilization (LMP), resulting in the induction of lysosome-mediated cell death through the release of lysosomal enzymes, including cathepsin, into the cytosol. Here we review the molecular mechanisms of LMP-mediated cell death and the enhancement of sensitivity to anticancer drugs. Induction of partial LMP increases apoptosis by releasing some cathepsins, whereas massive LMP and rupture induce non-apoptotic cell death through release of many cathepsins and generation of ROS and iron. Cancer cells have many drug-accumulating lysosomes that are more resistant to lysosome-sequestered drugs, suggesting a model of drug-induced lysosome-mediated chemoresistance. Lysosomal sequestration of hydrophobic weak base anticancer drugs can have a significant impact on their subcellular distribution. Lysosome membrane damage by LMP can overcome resistance to anticancer drugs by freeing captured hydrophobic weak base drugs from lysosomes. Therefore, LMP inducers or lysosomotropic agents can regulate lysosomal integrity and are novel strategies for cancer therapy.

• BMB Reports
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• v.41 no.12
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• pp.827-832
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• 2008

Many age-dependent neurodegenerative diseases are associated with the accumulation of abnormally folded proteins within neurons. One of the major proteolytic pathways in the cell is the autophagy pathway, which targets cytoplasmic contents and organelles to the lysosomes for bulk degradation under various physiological and stressful conditions. Although the importance of autophagy in cellular physiology is well appreciated, its precise roles in neurodegeneration remain largely unclear. Recent studies indicate that components of the endosomal sorting complex required for transport (ESCRT) are important in the autophagy pathway. Reduced activity of some ESCRT subunits leads to the accumulation of autophagosomes and failure to clear intracellular protein aggregates. Interestingly, rare mutations in CHMP2B, an ESCRT-III subunit, are associated with frontotemporal dementia linked to chromosome 3 (FTD3). Mutant CHMP2B proteins seem to disrupt the fusion of autophagosomes and lysosomes in cell culture models. These findings suggest a potential mechanism for the pathogenesis of FTD3 and possibly other neurodegenerative diseases as well.

• The Korean Journal of Zoology
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• v.21 no.3
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• pp.87-102
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• 1978

Electron microscopic studies were made to investigate changes in the fine structure of the liver, kidney and gills of Carassius carassius L. following exposure to 1 and 2.5 ppm of $HgCl_2$. The following results were obtained: 1. In the mercury-treated liver cells, an increase in the number of lysosomes were noticed. These lysosomes appeared to be of two types; round ones containing some crystalline structures and others with phagocytosed glycogen granules and mitochondria. Also observed were mitochondrial swelling where the matrix appeared less electrondense, and segregation of the nucleoli in the nucleus. 2. In the kidney, mercury treatment resulted in thickening of the basement membrane of the glomerulus, and appearance of vacuoles and cytoplasmic bodies in the proximal convoluted tubule. The vacuoles seemed to be formed from mitochondria. Nuclear shrinkage was also noticed at 2.5 ppm of $HgCl_2$. 3. Many large and small lysosomes appeared in response to mercury in the epithelial cells of the gill lamella. Also the lamellar membrane became fuzzy in appearance. 4. It can be concluded from these results that mercury-induced changes in the fine structure are associated with activation of detoxication processes and impairment of energy metabolism.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.4
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• pp.311-323
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• 2023

Ion homeostasis, which is regulated by ion channels, is crucial for intracellular signaling. These channels are involved in diverse signaling pathways, including cell proliferation, migration, and intracellular calcium dynamics. Consequently, ion channel dysfunction can lead to various diseases. In addition, these channels are present in the plasma membrane and intracellular organelles. However, our understanding of the function of intracellular organellar ion channels is limited. Recent advancements in electrophysiological techniques have enabled us to record ion channels within intracellular organelles and thus learn more about their functions. Autophagy is a vital process of intracellular protein degradation that facilitates the breakdown of aged, unnecessary, and harmful proteins into their amino acid residues. Lysosomes, which were previously considered protein-degrading garbage boxes, are now recognized as crucial intracellular sensors that play significant roles in normal signaling and disease pathogenesis. Lysosomes participate in various processes, including digestion, recycling, exocytosis, calcium signaling, nutrient sensing, and wound repair, highlighting the importance of ion channels in these signaling pathways. This review focuses on different lysosomal ion channels, including those associated with diseases, and provides insights into their cellular functions. By summarizing the existing knowledge and literature, this review emphasizes the need for further research in this field. Ultimately, this study aims to provide novel perspectives on the regulation of lysosomal ion channels and the significance of ion-associated signaling in intracellular functions to develop innovative therapeutic targets for rare and lysosomal storage diseases.