Biochemistry and membrane defense mechanisms
A lysosome contains over 60 types of lysosomal hydrolases—enzymes capable of breaking down biopolymers. An acidic environment is required for their efficient operation.
Specialized proton pumps ($H^+$-pumps) are present in the organelle membrane. Using ATP energy, they exchange intracellular sodium ions ($Na^+$) for hydrogen protons ($H^+$), pumping the latter into the vesicle.
Despite the aggressive environment, the lysosome is protected against autodigestion. The inner surface of its membrane is covered by a dense carbohydrate layer due to the high degree of glycosylation of membrane proteins.
Functions of lysosomes
The main task of the organelle is the intracellular digestion of macromolecules. Depending on the source of the digested material, two processes are distinguished:
- Autophagy: the process of cellular renewal. The cell's own damaged macromolecules and worn-out organelles are destroyed, which allows new components to be synthesized.
- Heterophagy: the breakdown of exogenous products of endocytosis. These can be nutrients or captured solid particles, including microorganisms, which ensures the nutrition and protection of the cell.
Traditional classification
Historically, the classification was based on the stage of the digestive process, which determines the morphology of the organelle.
- Primary lysosomes: newly formed vesicles. On electron micrographs, they have a homogeneous content and contain an initial set of yet-inactive enzymes.
- Secondary lysosomes: formed by the fusion of a primary lysosome with a substrate. They are larger, and their content is heterogeneous.
Among secondary structures, phagolysosomes (containing material from pino- or phagocytic vesicles) and autophagosomes (containing the cell's own structures, the number of which sharply increases during cell damage) are distinguished.
Modern concept: The endosomal pathway
The new terminology describes lysosome maturation through changes in pH levels. Primary lysosomes are now called hydrolase vesicles, and secondary lysosomes are termed lysosomes proper. "Proton vesicles" containing exclusively pumps for acidification are also distinguished.
Stages of the endosomal cycle:
- Early endosome: forms at the cell periphery from pinocytic vesicles. Its pH is neutral and corresponds to the extracellular environment.
- Late endosome: shifts deeper into the cytoplasm. By fusing with proton and hydrolase vesicles, it becomes acidified to pH 5.5–6.0, which triggers enzyme activation.
- Lysosome: massive influx of proton vesicles lowers the pH to < 5.0. Intensive hydrolysis begins.
Telolysosomes and the aging pigment
If the enzymes fail to completely break down the material, the process moves to its final stage.
- Telolysosomes (residual bodies): structures with incomplete hydrolysis. Their content becomes dense, and enzymatic activity is lost.
- Lipofuscin: the so-called "aging pigment." It is a complex inert protein-lipid conglomerate of undigested residues that has a brown color due to lipid peroxidation. It accumulates in long-lived cells incapable of division, such as neurons, muscle fibers, and cardiomyocytes.
In vivo, the operation of the lysosomal apparatus is often demonstrated using the India ink injection method. In whole-mount skin preparations, it can be seen that macrophages actively phagocytose the dye (blue granules—phagosomes and phagolysosomes—accumulate in the cytoplasm), whereas neighboring fibroblasts do not capture the ink.
Briefly: answers to topical questions
What classes of enzymes are contained in lysosomes?
Lysosomes contain about 60 types of hydrolytic enzymes (hydrolases) that break down macromolecules into monomers.
The following classes of hydrolases are present in lysosomes:
- Proteases — break down proteins.
- Nucleases — break down nucleic acids.
- Lipases — break down lipids.
- Glycosidases — break down carbohydrates.
- Esterases — break down esters.
Heterophagy is the digestion of foreign matter ("hetero" — a different substrate from outside). Autophagy is the digestion of one's own matter ("auto" — self, own organelles).
Class and exam questions
How is the lysosome protected from the action of its own enzymes?
The inner surface of its membrane is resistant to hydrolases due to a high degree of glycosylation—membrane proteins are covered with a layer of carbohydrates.
What is the difference between early and late endosomes?
The early endosome has a neutral pH. The late endosome, fusing with hydrolase and proton vesicles, is acidified to pH 5.5–6.0, after which enzyme activation begins within it.
What is lipofuscin?
This is a brown aging pigment consisting of a protein-lipid conglomerate of undigested residues. It accumulates in the form of telolysosomes in non-dividing cells (e.g., cardiomyocytes).
What else to study on this topic
- Molecular mechanism of membrane proton ATPases
- Differences in the formation of autophagosomes and phagolysosomes
- Lipid peroxidation processes during lipofuscin formation
- In vivo visualization of phagocytosis: histological differences between macrophages and fibroblasts
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