What is a Lysosome?

Lysosomes are organelles that break down biological macromolecules such as proteins, nucleic acids, and polysaccharides. The lysosome has a single-layer membrane with various shapes. It has a bubble-like structure of 0.025 to 0.8 microns. It contains many hydrolases. The function of the lysosome in the cell is to break down the substances that enter the cell from the outside. It can digest the local cytoplasm or organelles of the cell itself. When the cell ages, its lysosome ruptures, releasing hydrolase, digesting the entire cell and causing it to die. ^[1]

Lysosomes are round or oval, with different sizes, most of which are 0.2-0.8 m in diameter, 0.05 m in small ones, and several micrometers in large ones. It is surrounded by a unit film with a thickness of 7 to 10 nm.It contains more than 60 kinds of acid hydrolases, including proteases, nucleases, glycosidases, lipases, phosphatases, and sulfatase. The types and amounts of enzymes contained in lysosomes of different types of cells are also different. The optimal pH of the lysosomal hydrolase is 3.5 ~ 5.5, and the acidic environment in the lysosomal body is maintained by a special transporter (H pump) on the membrane ^[2]

Lysosome was first discovered in 1955. It is a vesicular organelle surrounded by a single layer of membrane and containing a variety of acid hydrolytic enzymes. Its main function is to perform intracellular digestion.

Heterogeneity, morphological size, and types of hydrolases contained may be very different,

There are two functions of lysosome: one is with

Primary lysosomes are formed in the form of buds on the trans surface of the Golgi apparatus. The formation process is as follows:

Endoplasmic network

Lysosomal silicosis

Silica dust particles (silica [x] dust) are ingested by macrophages after being inhaled into the alveoli, and phagosomes containing silica dust and lysosomes merge to form secondary lysosomes. The hydroxyl groups of silica form hydrogen bonds with phospholipids or proteins of the lysosomal membrane, causing the lysosomes of the phagocytic cells to disintegrate, the cell itself is also destroyed, the silicon dust is released, and then it is engulfed by other macrophages. This is repeated. . Damaged or damaged macrophages release "fibrogenic factors" and activate fibroblasts, resulting in the deposition of collagen fibers and fibrosis of lung tissue.

Lysosomal tuberculosis

Mycobacterium tuberculosis does not produce endotoxins or exotoxins. It is also free of capsules and invasive enzymes. However, the cerebroside component of the bacterial body can resist the intracellular bactericidal killing effect, which can cause a large number of Mycobacterium tuberculosis to grow and reproduce in the alveoli, causing macrophages to lyse. The released Mycobacterium tuberculosis is then swallowed and the above process is repeated, eventually causing lung tissue Calcification and fibrosis.

Lysosomal storage disease

Lysosome Storage Diseases (LSDs) are caused by genetic defects. Due to mutations in lysosomal enzymes and loss of function, large amounts of substrates are stored in lysosomes, which in turn affects cell function. Common storage disorders are mainly the following categories:

Tay-Sachs diesease: To be called black family familial dementia, the lysosome lacks amino-hexose esterase A (-N-hexosaminidase), leading to accumulation of ganglioside GM2 (Figure 6 -30), affect cell function, cause mental dementia, and die at the age of 2-6 years. The patient presents with progressive blindness, sickness, and paralysis, and the disease occurs primarily in the Jewish population.

Glycogen type II disease (Pompe disease or Pompe disease): lysosomal lack of alpha-1,4-glucosidase, glycogen accumulates in the lysosome, causing heart, liver, tongue enlargement and skeletal muscle Powerless. It is an autosomal defective genetic disease. Most of the patients are children and often die before the age of two.

Gaucher's disease (Gaucher's disease): Also known as cerebroside deposition disease, is caused by the lack of -glucosidase in the lysosomes of macrophages and brain nerve cells. A large amount of glucocerebroside is deposited in these lysosomes, macrophages become Gaucher cells, patients with enlarged liver, spleen, and lymph nodes, degenerative changes in the central nervous system, often die within 1 year of age.

Inclusion-cell disease (I-cell disease): A more severe storage disorder is caused by a single gene mutation in N-acetylglucosamine phosphotransferase. Due to the gene mutation, the M6P sorting signal cannot be formed on the lysosomal proenzyme processed in the Golgi apparatus, and the enzyme is transported out of the cell (default pathway). There is no hydrolytic enzyme in the lysosome of fibroblasts of this type of patients, which causes a large amount of substrate to be stored in the lysosome, forming what is called "inclusion". In addition, such patients have normal lysosomes in their liver cells, indicating that lysosomal formation also has pathways other than M6P.

Lysosomal hereditary disease

The synthesis of acid hydrolytic enzymes in lysosomes, like other proteins in the process of biosynthesis, is determined by genes. When genetic mutations cause obstacles to enzyme protein synthesis, lysosomal enzyme deficiency can result. Due to genetic defects in the body, a certain kind of hydrolase can be lacked in the lysosome, so that the corresponding substrate cannot be degraded and accumulated in the lysosome, resulting in cell metabolism barriers and the formation of lysosomal storage disease. The main pathological manifestations are lysosomal overload in the organs (liver, kidney, myocardium, and skeletal muscle), that is, cells that absorb too much or cannot digest substances, or because of reduced lysosomal enzyme activity, and the age of the body Grows, resulting in a large lysosomal accumulation in the cell causing overload. At present, more than 40 kinds of these diseases are known, and more than 30 kinds can be detected in China (see entry: lysosomal storage disease). Among them, glycogen storage disease type was first discovered. Due to a gene defect on the autosome of liver cells, the lack of -glucosidase in the lysosome leads to the inability of glycogen to be degraded into glucose, resulting in a large accumulation of glycogen in the liver and muscles. This disease mostly occurs in infants. The clinical manifestations are muscle weakness, enlarged heart, progressive heart failure, and death more than two years old, so the disease is also called cardiac glycogenosis.

Lysosomal rheumatoid arthritis

The etiology of rheumatoid arthritis is unknown, but the inflammatory changes in the periosteal tissue of the joint and the erosion of articular chondrocytes are thought to be caused by the local release of lysosomes in the cells. The reason may be that a certain rheumatoid factor, such as anti-IgG, is swallowed by macrophages, neutrophils, etc., and promotes the lysosomal enzyme to escape. Some of these enzymes, such as collagenase, can erode cartilage and cause local damage to the joints. Metabolites of cartilage digestion, such as chondroitin sulfate, can promote the production of kinins and participate in joint inflammation.

Lysosomal shock

During shock, the microcirculation of the body is disturbed, tissue ischemia and hypoxia affect the energy supply system, make the membrane unstable, cause leakage of lysosomal enzymes, and cause damage to cells and the body. The body's lysosomes increased in shock, volume increased, and phagosomes increased significantly. The enzymes in the lysosome are released inside and outside the tissue, mostly in the liver and mesentery, etc., causing the cells and tissues to autolyze. Therefore, in shock, measuring the level of lysosomal enzymes in lymph fluid and blood can be used as a quantitative indicator of the severity of cell damage. Acid phosphatase, -glucuronidase and cathepsin are usually used as indicators. Regarding the mechanism of lysosomal release during shock, it has been suggested that it is due to a decrease in pH and an obstruction of the tricarboxylic acid cycle. Hypoxia and ischemia during shock cause the pH of the cells to drop (about pH 5), acid hydrolytic enzymes are activated, and the lysosomal membrane is hydrolyzed, eventually leading to lysosomal membrane lysis and lysosomal release, resulting in autolysis of cells and tissues.

Lysosomal tumor

The relationship between lysosomes and tumors has attracted increasing attention. Generally, there are several views:

(1) Obstacles caused by carcinogens to regulate cell division and chromosomal aberrations may be related to the role of lysosomes in releasing hydrolases;

(2) Some substances that affect the permeability of lysosomal membranes, such as croton oil, certain detergents, hyperbaric oxygen, etc., are cofactors that promote carcinogenesis and can also cause abnormal cell division;

(3) In the case of a defective nuclear membrane, the nuclear membrane's protection of the nucleus is lost, and lysosomes can dissolve chromatin, causing cell mutation;

(4) certain products in the process of lysosomal metabolism are the material basis of tumor cell proliferation;

(5) Carcinogens enter cells and are always stored in lysosomes before integration with chromosomes, which has been confirmed by autoradiography.

In short, whether there is a direct relationship between lysosomes and tumorigenesis needs further exploration ^[2] .