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Autophagy

Аутофагия

Autophagy (from other Greek auto-som 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 undergo degradation in them.

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

Types and mechanisms of autophagy

Аутофагия
A: Autophagosome formation pattern: an insulating membrane surrounds cell structures and creates an autophagosome (AP), which fuses with the lysosome and creates an autolysosome (AL).
B: Electron micrograph of autophagosomal structures in the adipose body of Drosophila larva. C: Fluorescence-labeled autophagosomes in starving mouse liver cells

Three types of autophagy are now distinguished - microautophagy, macroautophagy and chaperone-dependent autophagy. With microautophagy, macromolecules and fragments of cell membranes are simply captured by the lysosome. In this way, the cell can digest proteins with a lack of energy or building material (for example, during starvation). But the processes of microautophagy occur under normal conditions and are generally indiscriminate. Sometimes during microautophagy, organoids are also digested; for example, microautophagy of peroxisomes and partial microautophagy of nuclei in which the cell remains viable is described in yeast.

In macroautophagy, a portion of the cytoplasm (often containing any organoids) is surrounded by a membrane compartment, similar to a cistern of the endoplasmic reticulum. As a result, this site is separated from the rest of the cytoplasm by two membranes. Such double-membrane organelles surrounding the removed organelles and cytoplasm are called autophagosomes. Autophagosomes bind to lysosomes to form autophagolysosomes, in which organelles and the rest of the contents of 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indiscriminate, although it is often emphasized that with the help of it the cell can get rid of organoids that have "outdated" (mitochondria, ribosomes, etc.).

The third type of autophagy is chaperone-mediated. In this method, directed transport of partially denatured proteins from the cytoplasm through the lysosome membrane to 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 chaperone and protein to be transported to the lysosome.

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

Autophagy regulation

Autophagy accompanies the vital activity of any normal cell in normal conditions. The main stimuli for enhancing the processes of autophagy in cells can serve

  • nutrient deficiency
  • the presence of damaged organelles in the cytoplasm
  • the presence in the cytoplasm of partially denaturing proteins and their aggregates

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

Currently, the genetic mechanisms that regulate autophagy are being studied in detail on yeast. Thus, the formation of autophagosomes requires the activity of numerous proteins of the Atg family (autophagosome-related proteins). Homologs of these proteins were found in mammals (including humans) and plants.

The importance of autophagy in normal and pathological processes

Autophagy is one of the ways to get rid of cells from unnecessary organelles, as well as the body from unnecessary 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 disrupted, and the destroyed cells are not removed, then the embryo most often becomes unviable

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

Disorders during autophagy can lead to inflammatory processes if parts of dead cells are not removed.

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

Autophagy: why 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 using special organelles, which de Duve called lysosomes. However, the mechanisms of autophagy became clear only after the experiments of Yoshinori Osuma (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 strains of yeast in which this process proceeded with a deviation from the norm.

This process was first described in 1963 by the Belgian biologist Christian de Duve, who observed how cells “digest” unnecessary substances using special organelles, which de Duve called lysosomes. However, the mechanisms of autophagy became clear only after the experiments of Yoshinori Osuma (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 strains of yeast in which this process proceeded with a deviation from the norm.

There are two ways for a cell to get rid of biological “trash.” First, she can take advantage of the huge molecules of ubiquitin protease, an enzyme that can break down proteins into individual amino acids. Proteases float freely in the cytoplasm. Osuma investigated the second method - the cleavage of "garbage" in lysosomes; it is called autophagy.

Аутофагия
Autophagy process: first around the object - molecules, parts of an organelle, organelle, bacterium or virus, a membrane forms. When it closes, the formed autophagosome transports the object to the lysosome and combines with it into the autolysosome, where the object is cleaved.

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

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

Via wikipedia.org & popmech.ru