Lysosomes

Lysosomes . Relatively large organelles , formed by the rough endoplasmic reticulum (RER) and then packaged by the Golgi complex, which contain hydrolytic and proteolytic enzymes that serve to digest materials of external (heterophagy) or internal (autophagy) origin that reach them. That is to say, they take care of cellular digestion . They have a very simple structure, “similar” to vacuoles , surrounded only by a membrane , they contain a large amount of digestive enzymes that degrade all the molecules that are useless for the cell .

Summary

[ disguise ]

• 1 Features
• 2 primary lysosomes
• 3 Secondary lysosomes
• 4 Lysosomal storage diseases
• 5 Source

Characteristics

Lysosomes are spherical vesicles , between 0.1 and 1 μm in diameter. They contain around 50 enzymes , generally hydrolytic, in acid solution; Enzymes need this acidic solution for optimal functioning. Lysosomes keep these enzymes separated from the rest of the cell , preventing them from chemically reacting with elements and organelles of the cell .

Lysosomes use their enzymes to recycle the different organelles of the cell , engulfing them, digesting them and releasing their components into the cytosol. This process is called autophagy, and the cell digests its own structures that are not necessary. The material is enclosed by vesicles that come from the endoplasmic reticulum and the Golgi apparatus, forming an autophagosome. When it joins the primary lysosome it forms an autophagolysosome and follows the same process as in the previous case.

In endocytosis, materials are collected from the outside of the cell and engulfed by endocytosis through the plasma membrane , which forms a phagosome. The lysosome joins the phagosome forming a phagolysosome and pours its contents into it, degrading the substances in the phagosome. Once hydrolyzed, the usable molecules pass into the cell to enter metabolic pathways and what is not necessary for the cell is discarded outside of it by exocytosis.

Lysosomes also release their enzymes out of the cell (exocytosis) to also degrade other materials. In view of its functions, its presence is high in white blood cells , because these have the function of degrading invading bodies.

Lysosomes are spherical or oval organelles that are located in the cell cytoplasm .

In electron microscopy they are easy to locate because it is the darkest organelle (the most stained) of those contained in the cytoplasm of the cell , while the mitochondria have a more grayish stain. The image on the right shows a partial image of the cell , the lysosomes have been marked with red arrows.

Lysosomes consist of a membrane that contains a cavity or lumen, it is a closed sac.

The content of lysosomes in a single cell is highly variable. Basically, the contents of a lysosome can appear homogeneous or heterogeneous.

When they are formed, lysosomes are loaded with enzymes with a hydrolytic function; This type of lysosome, known as a primary lysosome, may be the one that has a homogeneous appearance inside). From this, the lysosome is responsible for catabolizing most types of biochemical molecules in the cell .

Primary lysosomes

Primary lysosomes are organelles derived from the endomembrane system. Each primary lysosome is a vesicle budding from the Golgi apparatus, containing hydrolytic enzymes (hydrolases). Hydrolases are synthesized in the rough endoplasmic reticulum and travel to the Golgi apparatus by vesicular transport. There they undergo terminal glycosylation (a chemical process in which a carbohydrate is added to another molecule ) from which they result in carbohydrate chains rich in mannose-6-phosphate (mannose-6-P). Mannose-6-P is the molecular marker, the “stamp” that directs enzymes toward the lysosomal pathway. A disease has been studied in which hydrolases do not carry their marker; The membranes of the Golgi apparatus do not recognize them as such and package them into secretory vesicles to be exocytosed.

Those who suffer from this [disease] accumulate hydrolases in the extracellular environment, while their cells lack them.

The other forms (secondary lysosomes) are heterogeneous and can receive various names such as lysosomes with myelinated forms, multivesicular bodies, or residual bodies.

These types are produced by the storage in the lumen of the lysosome of substances that cannot be further degraded or by the transformation into lysosomes of other types of organelles such as autophagosomes and endosomes.

Secondary lysosomes

Primary lysosomes contain a variety of hydrolytic enzymes capable of degrading almost all organic molecules . These hydrolases come into contact with their substrates when primary lysosomes fuse with other vesicles . The fusion product is a secondary lysosome. Therefore, the digestion of organic molecules is carried out in secondary lysosomes, since these contain both the substrates and the enzymes capable of degrading them.

There are various forms of secondary lysosomes, depending on the origin of the vesicle that fuses with the primary lysosome:

• They arise from the fusion of the primary lysosome with a vesicle from phagocytosis, called the phagosome. They are found, for example, in white blood cells, capable of phagocytosing foreign particles that are then digested by these cells .
• late endosomes. They arise when primary lysosomes join with materials from early endosomes. Early endosomes contain macromolecules that enter by the mechanisms of nonspecific endocytosis and receptor-mediated endocytosis. The latter is used by cells to incorporate, for example, low-density lipoproteins or LDL.
• It is the product of the fusion between a primary lysosome and an autophagic vesicleor autophagosome. Some cytoplasmic organelles are enclosed in vesicles, with membranes that come from the cisternae of the endoplasmic reticulum, and are then recycled when these autophagic vesicles join with primary lysosomes.

What remains of the secondary lysosome after absorption is a residual body. Residual bodies contain indigestible waste that in some cases is exocytosed and in others not, accumulating in the cytosol as the cell ages. An example of residual bodies are lipofuscin granules seen in long-lived cells, such as neurons .

They are diseases caused by the dysfunction of some lysosomal enzyme or by the uncontrolled release of said enzymes into the cytosol, which produces cell lysis .

In some cases, the release of enzymes plays a physiological role, allowing the resorption of structures that are no longer useful, for example the tail of tadpoles during metamorphosis .

Lysosomal storage diseases

In lysosomal storage diseases, some lysosomal enzyme has reduced or no activity due to a genetic error and the substrate for said enzyme accumulates and deposits within the lysosome that increase in size due to undigested material, which interferes with the normal cellular processes; Some of these diseases are:

• They are diseases caused by the dysfunction of any of the enzymesin the sphingolipid degradation pathway. Since sphingolipids are abundant in the brain , several of these diseases cause severe mental retardation and premature death ; Among them we must highlight Tay-Sachs disease , Gaucher disease, Niemann-Pick disease, Krabbe disease, fucosidosis, etc.
• Lack of acid lipase. Acid lipase is a fundamental enzymein the metabolism of triglycerides and cholesterol , which accumulate in tissues. Dysfunction of this enzyme causes two diseases, cholesterol ester storage disease , in which the enzyme has very little activity, and Wolman’s disease, in which the enzyme is completely inactive.
• Glycogenosis type II or Pompe disease. It is a defect of α(1-4) lysosomal acid glucosidase, also called acid maltase. Glycogen appearsstored in lysosomes. In children it stands out for producing heart failure by accumulating in the heart muscle causing cardiomegaly. In adults the accumulation is more pronounced in skeletal muscle .
• Caused by the absence or malfunction of the enzymesnecessary for the degradation of molecules called glycosaminoglycans or glucosamineglycans (previously called mucopolysaccharides). They include mucopolysaccharidosis type I, also known as gargolism or Hurler’s disease , in which there is a defect in the enzyme α-1-iduronidase, and mucopolysaccharidosis type II or Hunter syndrome , caused by an error in the enzyme iduronate- 2-sulfatase.

In gout , uric acid from purine catabolism is produced in excess, causing the deposition of urate crystals in the joints. The crystals are phagocytosed by cells and accumulate in secondary lysosomes; These crystals cause the rupture of these vacuoles with the consequent release of lysosomal enzymes into the cytosol that cause the digestion of cellular components, the release of substances from the cell and cellular autolysis.