Role of lysosomes in physiological activities, diseases, and therapy

Abstract

Long known as digestive organelles, lysosomes have now emerged as multifaceted centers responsible for degradation, nutrient sensing, and immunity. Growing evidence also implicates role of lysosome-related mechanisms in pathologic process. In this review, we discuss physiological function of lysosomes and, more importantly, how the homeostasis of lysosomes is disrupted in several diseases, including atherosclerosis, neurodegenerative diseases, autoimmune disorders, pancreatitis, lysosomal storage disorders, and malignant tumors. In atherosclerosis and Gaucher disease, dysfunction of lysosomes changes cytokine secretion from macrophages, partially through inflammasome activation. In neurodegenerative diseases, defect autophagy facilitates accumulation of toxic protein and dysfunctional organelles leading to neuron death. Lysosomal dysfunction has been demonstrated in pathology of pancreatitis. Abnormal autophagy activation or inhibition has been revealed in autoimmune disorders. In tumor microenvironment, malignant phenotypes, including tumorigenesis, growth regulation, invasion, drug resistance, and radiotherapy resistance, of tumor cells and behaviors of tumor-associated macrophages, fibroblasts, dendritic cells, and T cells are also mediated by lysosomes. Based on these findings, a series of therapeutic methods targeting lysosomal proteins and processes have been developed from bench to bedside. In a word, present researches corroborate lysosomes to be pivotal organelles for understanding pathology of atherosclerosis, neurodegenerative diseases, autoimmune disorders, pancreatitis, and lysosomal storage disorders, and malignant tumors and developing novel therapeutic strategies.

Trafficking of Full-Length and N-Terminally Truncated Cathepsin B in Human Colorectal Carcinoma Cells

“…N-terminally truncated forms have also been reported for other cathepsins, such as cathepsin H in human prostate cancer cells [29], cathepsin L in embryonic fibroblasts [30], or breast carcinoma cells [31], and in cathepsin L2/V in thyroid epithelial cells [32]. Thus, according to present information available, most of the N-terminally truncated forms of cysteine cathepsins are associated with pathological conditions, more evidently with cancer [8,12,[16][17][18][32][33][34].…”

Ion Interference Therapy of Tumors Based on Inorganic Nanoparticles

“…H + ions are widely distributed inside and outside cells to regulate the survival microenvironment of cells and the acid–base balance in cells. In particular, the acidic organelle in cells, the lysosome, as a proton store, is the center responsible for degradation, nutrient sensing and immunity [ 18 ]. At the same time, lysosomes are also closely related to the growth, proliferation and migration of tumor cells [ 19 ].…”

Relationship between lysosomal dyshomeostasis and progression of diabetic kidney disease

“…Upon lysosomal injury, galectin 9 increases the association with lysosomal glycoproteins, whereas it decreases interactions with the deubiquitinase USP9X; K63 ubiquitination of TAK1 activates AMPK in damaged lysosomes 22 , 23 . Furthermore, lysosomes also participate in immune processes 24 and form exosomes 25 .…”