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Autophagy

Аутофагия

Autophagy (from the ancient Greek auto-self and “is”) is a process in which the internal components of a cell are delivered inside its lysosomes (in mammals) or vacuoles (yeast cells) and are degraded in them.

The word "autophagy" means "eating itself." This is a built-in mechanism for recycling waste - unnecessary proteins, old, worn cells and other waste biomaterial, as well as bacteria and viruses destroyed by the immune system. Without this process, our cells would have died under an avalanche of dead bacteria and viruses, spent their proteins and worn organelles.

Types and mechanisms of autophagy

Аутофагия
A: Scheme of autophagosome formation: the insulating membrane surrounds cellular structures and creates an autophagosome (AP), which fuses with the lysosome and creates an autolysosome (AL).
B: Electron micrograph of autophagosome structures in the fat body of Drosophila larvae. C: Fluorescently labeled autophagosomes in liver cells of a starving mouse

Now there are three types of autophagy - microautophagy, macroautophagy and chaperone-dependent autophagy. In microauthophagy, macromolecules and fragments of cell membranes are simply captured by the lysosome. In this way, the cell can digest proteins when there is a shortage of energy or building material (for example, when fasting). But microautophagy processes occur under normal conditions and are generally non-selective. Sometimes organoids are digested during microautophagy; Thus, in yeast, microautophagy is described by peroxisome and partial microautophagy of nuclei, in which the cell retains viability.

In macroautophagy, the area of ​​the cytoplasm (often containing any organelles) is surrounded by a membrane compartment similar to the cistern of the endoplasmic reticulum. As a result, this area is separated from the rest of the cytoplasm by two membranes. Such two-membrane organelles surrounding the removed organelles and the cytoplasm are called autophagosomes. Autophagosomes combine with lysosomes to form autophagolysosomes, in which the organelles and the rest of the autophagosomes are digested.

Apparently, macroautophagy is also indiscriminate, although it is often emphasized that with the help of it, the cell can get rid of organisms which have served their time (mitochondria, ribosomes, etc.).

The third type of autophagy is chaperone-mediated. In this method, directional transport of partially denatured proteins from the cytoplasm through the lysosome membrane into its cavity occurs, where they are digested. This type of autophagy, described only for mammals, is induced by stress. It occurs with the participation of cytoplasmic chaperone proteins of the hsc-70 family, auxiliary proteins and LAMP-2, which serves as a membrane receptor for the complex of the chaperone and protein to be transported to the lysosome.

In an autophagic type of cell death, all the organelles of the cell are digested, leaving only the cellular debris absorbed by macrophages.

Regulation of autophagy

Autophagy accompanies the vital activity of any normal cell under normal conditions. The main incentives to enhance the processes of autophagy in cells can be

  • nutritional deficiencies
  • presence of damaged organelles in the cytoplasm
  • the presence in the cytoplasm of partially denaturated proteins and their aggregates

In addition to starvation, autophagy can be induced by oxidative or toxic stress.

At present, genetic mechanisms regulating autophagy are studied in detail on yeast. Thus, for the formation of autophagosomes, the activity of numerous proteins of the Atg-family (autophagosome-related proteins) is necessary. Homologs of these proteins are found in mammals (including humans) and plants.

The value of autophagy in normal and pathological processes

Autophagy - one of the ways to get rid of cells from unwanted organelles, as well as the body from unwanted cells.

Autophagy is especially important in the process of embryogenesis, with the so-called self-programmed cell death. Now this variant of autophagy is more often called caspase-independent apoptosis. If these processes are disturbed and destroyed cells are not removed, then the embryo most often becomes unviable.

Sometimes, due to autophagy, the cell can compensate for the lack of nutrients and energy and return to normal life. On the contrary, in the case of the intensification of autophagy processes, the cells are destroyed, and in many cases, connective tissue takes their place. Such disorders are one of the causes of heart failure.

Disruptions in the process of autophagy can lead to inflammatory processes if parts of the dead cells are not removed.

A particularly large (though not fully understood) role in autophagy disorders is played in the development of myopathies and neurodegenerative diseases. Thus, in Alzheimer's disease, the processes of neurons in the affected areas of the brain show an accumulation of immature autophagosomes that are not transported to the cell body and do not merge with lysosomes. Mutant huntingtin and alpha synuclein - proteins, the accumulation of which in neurons causes, respectively, Huntington's disease and Parkinson's disease - are absorbed and digested during chaperone-dependent autophagy, and the activation of this process prevents the formation of their aggregates in neurons.

Autophagy: for which they gave the Nobel Prize in medicine

Аутофагия

This process was first described in 1963 by the Belgian biologist Christian de Duve, who observed how cells “digest” unnecessary substances with the help of special organelles, which de Duve called lysosomes. However, the mechanisms of autophagy became clear only after Yoshinori Osuma's experiments (he currently works at the Tokyo Institute of Technology in Yokohama). To determine which genes are responsible for the course of autophagy, Osuma experimented with yeast strains in which this process was abnormal.

This process was first described in 1963 by the Belgian biologist Christian de Duve, who observed how cells “digest” unnecessary substances with the help of special organelles, which de Duve called lysosomes. However, the mechanisms of autophagy became clear only after Yoshinori Osuma's experiments (he currently works at the Tokyo Institute of Technology in Yokohama). To determine which genes are responsible for the course of autophagy, Osuma experimented with yeast strains in which this process was abnormal.

The cell has two ways to get rid of biological "garbage". First, it can take advantage of the huge molecules of ubiquitin protease, an enzyme that can break down proteins into individual amino acids. Proteases swim freely in the cytoplasm. Osuma investigated the second method - the splitting of "garbage" in the lysosomes; it is called autophagy.

Аутофагия
The process of autophagy: first around the object - molecules, parts of organelles, organelles, bacteria or virus, a membrane is formed. When it closes, the resulting autophagosome transports the object to the lysosome and combines with it into an autolysosome, where the object splits.

Autophagy is realized as follows: first, the cell sequesters (isolates) the molecules to be destroyed, building a membrane around them. The resulting quasi-organella with a molecule enclosed in it or even another organelle is called an autophagosome. Then the autophagosome approaches the lysosome, forming the autolysosome. Inside it, an isolated object is exposed to hydrolases - enzymes that dissolve it.

Autophagy is a normal part of the cell life cycle. It ensures cell survival during fasting, makes possible cell differentiation and growth control, and also participates in the regulation of many other processes in the cell. Improper course of autophagy is associated with the development of Parkinson's disease, type 2 diabetes, and other diseases. However, the practical application of the discovery Osumi and his colleagues have not yet found.

Via wikipedia.org & popmech.ru