"Nobel Prize" in medicine – 2016: details

Nobel Prize in Medicine and Physiology 2016: for self-eating

Viktor Lebedev, "Biomolecule"

In 2016, the Nobel Prize in Physiology and Medicine was awarded to Professor Yoshinori Osumi of the Tokyo Institute of Technology. The Japanese scientist was awarded it for his fundamental works that explained to the world how autophagy occurs – a key process of processing and reutilization of cellular components. (Autophagy in Greek means "eating yourself" or "self-eating".)

Yoshinori Osumi became the fourth Japanese to be awarded the Nobel Prize in Medicine and Physiology. The first was Suzumi Tonegawa: for the discovery of the genetic principle of the formation of various antibodies. Then in 2012, Shinya Yamanaka received the award for his work with induced stem cells, as biomolecule has already written [1]. A year ago, the winner of the award was Satoshi Omura, who put into the hands of doctors a new weapon to fight parasitic worms that cause diseases in humans [2]. It is interesting that in such a short period of time, three prizes went to the Land of the Rising Sun at once.

Autophagy, for the study of which the prize was awarded this year, is a set of processes that allow a cell to get rid of accumulations of intracellular "garbage" and organelles that have become unusable with the help of lysosomes [3]. During autophagy, the cell component that is destined to be destroyed is surrounded by a two-layer membrane, forming an autophagosome. At the next stage, the lysosome merges with the autophagosome, and lysosomal enzymes begin to break down the contents of the autophagosome to the smallest molecules. So the cell destroys old or defective components, and the "remains" are reused. The Nobel Prize in Physiology or Medicine was also awarded for the discovery of lysosomes at the time: in 1974, it was received by the Belgian Christian de Duve [4]. He, by the way, coined the term "autophagy" in 1963. So, in a certain sense, the prize awarded this year has its own "Nobel" history.

The process of autophagy itself has been known since the 1960s, but its molecular basis remained unclear to scientists. To study how autophagy proceeds, Osumi chose the usual baker's yeast Saccharomyces cerevisiae (Fig. 1).

Figure 1. Yeast Saccharomyces cerevisiae are the main characters of the Nobel Prize after the laureate himself. Drawing from the website tangledwing.tumblr.com .

In the experiment, he used not simple, but mutant yeast cells: they were deprived of several proteolytic enzymes. In addition, scientists additionally stimulated autophagy by placing cells in an environment poor in nutrients (and it was believed that the cell begins to engage in "self-eating" precisely in conditions of starvation). Autophagosomes began to appear in the cytoplasm of the cell, and after three hours the yeast vacuoles were completely filled with them (Fig. 2). Scientists examined the formed organelles, and it turned out that they did not differ in composition and chemical activity from the cytoplasm surrounding them. This meant that the autophagy process was suspended due to a lack of proteolytic enzymes [5]. They were supposed to come from lysosomes, but due to a genetic defect, the enzymes were not synthesized by the cell.

Figure 2. A yeast cell with a vacuole filled with autophagosomes in which there is no splitting of the contents. The letter V denotes a vacuole, and the letters AB denote autophagosomes that have not merged with lysosomes. Figure from [5].

In the same work, data were published that the absence of the enzyme proteinase B encoded in the PRB1 gene played a key role in blocking autophagy in yeast. A year later, data on 15 key genes involved in autophagy were published [6]. Further research conducted with colleagues by Yoshinori Osumi revealed a complex cascade of biochemical reactions that allows yeast cells to start the process of autophagy [7].

Thanks to the work of Yoshinori Osumi, other scientists have received tools to study autophagy not only in yeast, but also in other living beings, including humans. In the course of further research, it was found that autophagy is a conservative process, and in humans it occurs in approximately the same way. With the help of autophagy, the cells of our body receive the missing energy and building resources, mobilizing internal reserves. Autophagy is involved in the removal of damaged cell structures, which is important for maintaining normal cell function. Also, this process is one of the mechanisms of programmed cell death. Disorders of autophagy may underlie cancer and Parkinson's disease. In addition, autophagy is aimed at combating intracellular infectious agents, for example, the causative agent of tuberculosis. Perhaps due to the fact that yeast once revealed to us the secret of autophagy, we will get a cure for these and other diseases.

Literature

1. Biomolecule: "Nobel Prize in Physiology or Medicine (2012): induced stem cells";
2. Biomolecule: "Winners of the 2015 Nobel Prize in Physiology and Medicine have been named";
3. biomolecule: "Autophagy, protophagy and the rest";
4. The Nobel prize in physiology or medicine 1974. Website of the Nobel Committee;
5. Takeshige K., Baba M., Tsuboi S., Noda T., Ohsumi Y. (1992). Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. J. Cell. Biol. 119, 301–311;
6. Tsukada M. and Ohsumi Y. (1993). Isolation and characterization of autophagy-defective mutants of Saccharomyces cervisiae. FEBS Lett. 333, 169–174;
7. Mizushima N., Noda T., Yoshimori T., Tanaka Y., Ishii T., George M.D. et al. (1998). A protein conjugation system essential for autophagy. Nature. 395, 395–398.

Portal "Eternal youth" http://vechnayamolodost.ru  04.10.2016