What do antibiotics threaten us with

De-energized cell

Yuri Drize, "Search"

It sounds so beautiful - mitochondria (from the Greek. μίτος – thread and χόνδρος - grain, grain)! These tiny intracellular formations, organelles, are present in almost all cells except bacterial ones. The simplest parasite has them, and the decoration of nature – man, there are many of them in each of his cells. The young scientist Pyotr Kamensky began studying them while studying at the biology faculty of Moscow State University and continues today, becoming a leading researcher at the Faculty of Biology of Moscow State University and a candidate of Sciences.

– It is believed that about a billion years ago, mitochondria were free–living bacteria, - says Peter Andreevich. – At some point, an ordinary event happened: one bacterium - our mitochondria - swallowed another (this happens all the time with them). And then something strange happened: the "victim" bacterium resisted eating and began to live its own special life inside the "hostess". In a sense, a symbiosis began, since the hostess was also quite satisfied with this situation. The bacteria adapted to each other – and in the process of evolution, they healed in peace and harmony inside the cell. She just needs them – this is a kind of her power station. The energy required for cell life is produced by mitochondria in the form of ATP molecules. As a result, it is mitochondria that give energy to the cells of a worm or a person. And the processes taking place in them are extremely interesting to me, a molecular biologist.

But mitochondria have an enemy not of organic origin, but created by man for his own protection – these are antibiotics. Mitochondria are a target for them, which they hit. And people do not even suspect that they are de-energizing themselves. We drink antibiotics for elementary flu, although the virus causes it and these drugs are powerless against it, and for any inflammation. Antibiotics enter the cells, suppress the mitochondria – and the cell does not feel well. In our philistine language, this is called a "side effect". The kidneys and liver are almost the first to suffer from it – their work is disrupted.

– As they say, one heals, the other cripples?

– Partly so. What is an antibiotic? This is a certain molecule with a specific chemical structure. Most antibiotics act on bacterial ribosomes – large molecular complexes that are engaged in protein biosynthesis – one of the main processes occurring in cells. Antibiotics stick to the bacterial ribosome, literally "hang" on it and do their job – kill it. And it is necessary to achieve, and this should become the main task, that they bypass the mitochondrial ribosomes without affecting or destroying them. In antibiotics, this needs to be "fixed" first.

– There is an opinion that these drugs are obsolete. More effective methods are being developed, for example, targeted drug delivery. So is it worth improving antibiotics?

– Indeed, antibiotics have a number of disadvantages, for example, they kill intestinal microflora – beneficial bacteria living in the human body. In addition, harmful bacteria get used to them – as a result, antibiotics lose their "killing power". Everything is so. But before the advent of new drugs and technologies, it is still possible to live and live, so it is impossible to give up antibiotics today. It's just that they need to change something, improve. And to begin with, we should properly study the mechanisms of protein synthesis in mitochondria, which we still know very poorly.

While researching baker's yeast, beloved by housewives, we discovered an unknown protein factor that is extremely important for protein synthesis occurring in mitochondria: It turned out that the Aim23 protein is a multifunctional regulator of the entire synthesis process. If it is removed, then there will be an effect that has never been noticed before – a kind of imbalance of synthesis will occur. And the mitochondria will lose the function of a "power station". However, as we were able to establish for the first time, over time, the mitochondria still manages, having adapted to a critical situation, to balance proteins again and start producing energy again. It remains to find out the nature of the action of this most subtle mechanism, to understand what should be done so as not to disrupt its work. This is only the first step, so it is hardly possible to use the knowledge gained for practical purposes. But in the future, I am sure, it will be possible to create more advanced antibiotics without strong side effects. We need antibiotics that would still suppress bacterial factors, but would not affect our mitochondria. Let's note one more point. In order to "bring to mind" an antibiotic, it is primarily tested in so-called in vitro systems (that is, in a test tube, not in a living cell). If we really want to create antibiotics that will not affect mitochondrial translation, we cannot do without a "test tube" system of this process. And the system of mitochondrial translation in vitro still does not exist. Why haven't scientists been able to do it yet? This, as they say, is not a Newton binomial. To assemble such a complex system from individual components brick by brick, you need to at least get to know them all to one. Thus, the discovery of each new factor of mitochondrial translation significantly brings us closer to the successful modeling of this process "in vitro". And when such a model is made, it will be much easier to modify antibiotics.

We wrote an article about the mechanism we discovered and published it in the journal Scientific Reports, the publishing house Nature Publishing Group (Aim-less translation: loss of Saccharomyces cerevisiae mitochondrial translation initiation factor mIF3/Aim23 leads to unbalanced protein synthesis – VM). It has a fairly high impact factor of 6, and since the journal is interdisciplinary, it enjoys quite a lot of popularity among scientists around the world. The article was published in early January, very little time has passed, but we are already being quoted, so I hope our work will be noticed, since we have described an unusual feature of mitochondrial translation, which was not discovered before us. And for the first time they showed the leading role of one of the proteins involved in synthesis. This came as a complete surprise to scientists and aroused their interest. We hope that the new knowledge will help to get not only new generation antibiotics. It is known that mutations can occur in a human protein similar to the yeast Aim23, with which we worked, and that in some way, it is still unclear how, they are associated with the development of Parkinson's disease. And the more we learn about this amazing protein, the more likely it is that over time we will be able to explain this phenomenon and try to approach the treatment of this terrible disease.

In a sense, our work has opened the doors to the unknown: in addition to the answers received in it, a lot of new questions arise. However, there is hope, and this, in my opinion, is the main thing: if we are able to understand the complex processes occurring in mitochondria and find out the role of Aim23 in the cell, we may understand how the occurrence of Parkinson's disease is associated with this protein.

Portal "Eternal youth" http://vechnayamolodost.ru  10.05.2016