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Cellular autophagy. Dormancy, apoptosis or autophagy: how the cell makes the decision

On average, a kilogram of potato chips costs two hundred times more than a kilogram of potatoes.

Lately I've been getting more and more questions about autophagy. At first, such a wave of interest in molecular biology surprised me. But it turned out that the fact is that various “nutrition coaches” recommend taking long breaks between meals, something like fasting for 14-16 hours and call this process autophagy.

Allegedly, during such fasting, the body processes old, sick, damaged cells and creates new ones from them - young and healthy. And allegedly it was for the invention of such a “diet” that the Japanese scientist Yoshinori Ohsumi received the Nobel Prize.

To put it mildly, all these stories are not true. But it seems to me that a short answer in this situation is not enough. So let's look into it in detail.

Yoshinori Ohsumi actually exists, he is a biologist who works in the field of molecular biology. And he actually received the Nobel Prize for “elucidating the mechanism of autophagy, self-phagocytosis, in which hungry cells use their own proteins as a source of nutrition.” But this has nothing to do with losing weight and rejuvenating the body at all. I think Mr. Osumi would be very surprised if he learned about such an interpretation of his work.

What is autophagy

This is a mechanism found in the cells of eukaryotic organisms, from yeast to humans, that prevents the accumulation of abnormal amounts of protein in the cell, allowing proteins to be recycled when they are oversynthesized. In the case of starvation, the destruction of cellular components promotes cell survival by maintaining cellular energy levels.

Autophagy is involved in maintaining the homeostasis of living organisms by eliminating pathogenic microorganisms that have invaded the cytoplasm.

In disease, autophagy is considered in some cases as an adaptive response to stress that promotes survival, and in others, it contributes to cell death and disease (Alzheimer's disease, coronary artery disease, etc.).

How autophagy works on an organismal scale

In order for cells to perform vital functions, the body needs to synthesize proteins, which consist of amino acids. That is, in order for cells to function normally, essential amino acids are needed to serve as a source of nutrients.

During fasting, when nutrients are depleted and amino acids are cut off, the body can suffer serious damage due to cell death. However, it is believed that cells can temporarily avoid this damage through autophagy.

When autophagy occurs, some of the protein that is always present in the cell is broken down to form peptides or amino acids. However, avoiding hunger through autophagy is temporary and may not help if hunger continues for a long time. And when autophagy progresses excessively, it leads to cell death.

The role of autophagy in the prevention and promotion of diseases

As is already clear from what was written above, autophagy cannot be called a process that is clearly beneficial or clearly harmful. It all depends on the specific situation and intensity of the process.

For example, autophagy plays an important role in cancer. And the role can be completely opposite. It can both protect against cancer by destroying potentially dangerous cells, and promote the progression of cancer by helping tumor cells survive.

Autophagy is harmful in Alzheimer's disease. Researchers from the RIKEN Center in Japan have found that the absence of autophagy in neurons prevents the secretion of beta-amyloid and the formation of amyloid plaques in the brain. The same data was obtained by researchers from the University of Zaragoza.

But in the hereditary form of Parkinson's disease, on the contrary, the absence of autophagy causes the accumulation of components that cause the death of neurons.

Autophagy affects cardiovascular diseases both positively and negatively. In the early stages of hypertension, for example, autophagy helps restore tissue faster, but if over-activated, it can increase tissue damage. Especially considering that the regenerative capacity of myocardial tissue is extremely limited.

Since disruption of the autophagy process is involved in the pathogenesis of a wide range of diseases, scientists around the world are making great efforts to identify or create drugs that will be able to regulate it. Not only speed up, but also slow down or even stop.

What does autophagy have to do with weight loss and rejuvenation?

Definitely not for weight loss. In the context of nutrition, autophagy is a mechanism that, during fasting, heavy physical activity, etc., allows you to maintain homeostasis. We can say that thanks to autophagy, the body can starve harmlessly for some time, receiving the necessary amino acids from its own tissues. That is, this is a function that preserves the life of the body during interruptions in receiving food.

Since excess weight is by no means excess proteins, but excess fat, it is absolutely incomprehensible how adherents of “autophagy for weight loss” generally connected this process with weight loss.

Rejuvenation is also a problem. The fact that one cell has died does not mean that the new one formed in its place will be of better quality, and no one can guarantee that it will not be a malignant tumor cell.

Although, of course, one should not discount the fact that dysfunction of the autophagy process plays a role in many age-related diseases. For example, scientists were able to increase the lifespan of nematodes and fruit flies by increasing autophagy. But given the difference in nematode and human physiology and the role of autophagy in neurodegenerative and cardiovascular diseases, it cannot be said that the same methods will lead to an increase in human lifespan.

In general, in order to draw any conclusions about the effect of the autophagy process on lifespan, we will have to wait until researchers comprehensively study this process and receive unambiguous answers.

Summarizing the above, only one thing can be said. There has never been a “miracle pill” for weight loss. To lose weight, feel better and look younger, you need to use the simple old way - eat right, exercise and get enough sleep.

Mechanisms of autophagy activation - Nobel Prize in Medicine 2016

Winner of the 2016 Nobel Prize in Medicine, Dr. Ohsumi shows us that intermittent fasting can give us longer and healthier lives. Find out how cellular autophagy can add ten healthy years to your life.

Did you hear that Dr. Yoshinori Ohsumi won the Nobel Prize this year for his work on the “self-eating” of body cells?

“Why would cells eat themselves?” Could you ask.

“To live longer and healthier,” I might answer.

Let me explain.

Cells don't actually eat themselves completely. They only partially break down proteins and non-essential components to reuse them for energy. Cell biologist Dr. Ohsumi received Nobel Prize in Medicine in 2016, because his work on cellular autophagy gives us greater clarity about how the body's cells get rid of toxins and repair themselves.

This process is called "cellular autophagy", and this is what you need your own cells to do on a regular basis. That is, if you want to increase your chances of living a long, healthy life without long-term illnesses.

What is cellular autophagy?

Cellular autophagy is an essential process for the body to survive and stay healthy. During a period when a person is restricting caloric intake, or completely starving Not only do cells break down proteins and non-essential components to reuse them for energy, but cells also use autophagy to:

  • Destruction of foreign viruses and bacteria; (now you probably understand why you don’t feel like eating when you have a cold or flu?), and also
  • Rid yourself of damaged structures; a process that repairs damage that may contribute to the development of cancer, infectious diseases, immunological diseases and neurodegenerative diseases; including Parkinson's disease, type 2 diabetes.

Another fact is that interruptions in the functioning of autophagy mechanisms play a role in aging; vice versa, improving autophagy is believed to slow down the aging process.

So this autophagy topic is a very exciting topic (received even a Nobel Prize!) It is very important, in fact it was discovered back in the 60s of the last century, but little was known about how autophagy actually occurs , which genes are involved, and its specific role in disease and normal development before the research of Dr. Ohsumi, who began to study autophagy in yeast. He has been studying autophagy for 27 years.

Yes, that same yeast again! The point is, however, that Dr. Ohsumi's pioneering work demonstrates that autophagy genes and metabolic pathways in yeast are similar in higher organisms, including humans.

The word "autophagy" comes from two Greek words meaning "self-eating." This refers to a process in which cellular debris is captured and sealed into sac-like membranes called autophagosomes. The sealed contents are transported to another structure called a lysosome, the equivalent of a cell's trash bin.

By studying the process in yeast cells, Dr. Ohsumi identified the major genes involved in autophagy and showed which proteins they code for together to build the autophagosomal membrane. He later showed that a similar process occurs during cell communication recycling in human cells - and that our cells would not survive without this process.

Autophagy removes cholesterol buildup in human artery walls

This picture illustrates a discovery made by a team of researchers from the University of Ottawa Heart Institute, led by biochemist Yves Marcel, director of the High Density Lipoprotein Biology Laboratory at the Heart Institute of Canada.

Dr. Marcel and his team have discovered another function cellular autophagy- mobilization and removal of cholesterol from cells.

Research from the Canadian Heart Institute has shown that autophagy can absorb and digest cholesterol that accumulates in artery walls. “This process promotes the elimination of cholesterol and may help find entirely new ways to prevent the development of atherosclerosis, which is a leading cause of heart attacks and strokes,” says Dr. Yves Marcel.

History of the use of therapeutic intermittent fasting

The awarding of the Nobel Prize in 2016 for research in the field of autophagy renewed interest in the topic of intermittent fasting. Many people of the older generation born in the USSR remember the method of therapeutic fasting from the 70s of the last century, when it was made popular by Paul Breguet’s book “The Miracle of Fasting.” But the positive effect of fasting on health has been known since very ancient times - it is mentioned 74 times in the Bible! Many famous philosophers and scientists of antiquity starved: the greatest mathematician Pythagoras, the philosophers Socrates and Plato, and they all lived quite a long time - around 90–100 years.

In the USSR, the topic of therapeutic fasting was studied by Doctor of Medical Sciences Yuri Nikolaev, in 1973 he published the popular book “Fasting for Health” - it sold out instantly, the circulation was 200 thousand copies, the book was translated into many foreign languages. For more than 10 years, Nikolaev studied the effect of fasting on various human diseases and as a result, his method called “fasting-dietary therapy” (RDT) appeared. The method was so popular in the USSR that hospitals even opened departments dedicated specifically to this method of treatment. I don’t know why the technique was forgotten in our country - most likely it is due to the collapse of the USSR, like many other things. Doctor of Medical Sciences Yuri Nikolaev himself died in 1998 at the age of 93.

Intermittent fasting to activate autophagy

Well, now let's move on to practice. The great news is that you can choose intermittent fasting technique to trigger autophagy which best suits you:

  • Eat between 1:00 pm and 8:00 pm, giving your body 17 hours without food to increase autophagy processes; or
  • Eat as usual for five days a week, and limit calories to 500 two days a week (have fasting days on vegetables); or
  • Eat as usual for five days a week, but limit calories to 500 by eating only raw vegetables for one day and completely fast for one day.

Data types intermittent fasting have proven effective in activating autophagy in laboratory animals, and also in humans in which biomarkers responsible for the risk of developing cancer, diabetes and heart disease have decreased.

If you adhere to a vegetarian diet, then periodic fasting is probably not necessary for you, since with this type of diet, autophagy is most likely activated due to constant calorie restriction, of course, if you do not eat only sweet fruits - the so-called fruitarianism, in my opinion Looks like a very harmful way of eating for human health.

In my article, I cited the BBC documentary “Eat, Fast, Live Longer,” which talked about some options for fasting and caloric restriction diets, I recommend watching the film, it’s really very interesting. In it, the main character visits several centers for the study of fasting, and applies it to himself, choosing the most suitable one for himself.

Conclusion: in the article I talked about how you can improve your health by intermittent fasting activates the autophagy process in the body, it is one of the most important things you can do for your health and longevity, along with taking and giving up bad habits.

Thank you for reading my article, what do you think about starvation? Have you ever tried fasting? Write your comments after the article, I will be interested to hear about your experience.

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Roman Zabolotnikov

For more than five years I have been helping readers of this site obtain the latest information on the topic of biohacking, improving health, prolonging youth and achieving longevity, and also sharing personal experience and practical experience in the field of using supplements and drugs with IHERB. I would be grateful if you take a few minutes and leave your comments and questions about the article you read; your opinion is very important to make this site more interesting and the materials more understandable.

Types and mechanisms of autophagy

There are now three types of autophagy: microautophagy, macroautophagy and chaperone-dependent autophagy. During microautophagy, macromolecules and fragments of cell membranes are simply captured by the lysosome. In this way, the cell can digest proteins when there is a lack of energy or building material (for example, during starvation). But microautophagy processes also occur under normal conditions and are generally non-selective. Sometimes organelles are also digested during microautophagy; Thus, microautophagy of peroxisomes and partial microautophagy of nuclei, in which the cell remains viable, have been described in yeast.

In macroautophagy, a region of cytoplasm (often containing some kind of organelle) is surrounded by a membrane compartment similar to the endoplasmic reticulum tank. As a result, this area is separated from the rest of the cytoplasm by two membranes. Such double-membrane organelles surrounding the excised organelles and cytoplasm are called autophagosomes. Autophagosomes combine with lysosomes to form autophagolysosomes, in which the organelles and the rest of the contents of the autophagosome are digested.
Apparently, macroautophagy is also nonselective, although it is often emphasized that with its help the cell can get rid of “outdated” organelles (mitochondria, ribosomes, etc.).
The third type of autophagy is chaperone-mediated. With this method, the directed transport of partially denatured proteins from the cytoplasm occurs through the lysosome membrane into its cavity, where they are digested. This type of autophagy, described only in 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 into the lysosome.
In the autophagic type of cell death, all organelles of the cell are digested, leaving only cellular debris that is absorbed by macrophages.

Regulation of autophagy

Autophagy accompanies the life of any normal cell under normal conditions. The main stimuli for enhancing autophagy processes in cells can be

  • lack of nutrients
  • the presence of damaged organelles in the cytoplasm
  • the presence of partially denatured proteins and their aggregates in the cytoplasm

In addition to starvation, autophagy can be induced by oxidative or toxic stress.
The genetic mechanisms regulating autophagy are currently being studied in detail in yeast. Thus, the formation of autophagosomes requires the activity of numerous proteins of the Atg family (autophagosome-related proteins). Homologs of these proteins have been found in mammals (including humans) and plants.

The importance of autophagy in normal and pathological processes

Autophagy is one of the ways to rid cells of unnecessary organelles, as well as the body of unnecessary cells.
Autophagy is especially important during embryogenesis, during the so-called self-programmed cell death. Nowadays, 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 non-viable.
Sometimes, thanks to autophagy, the cell can compensate for the lack of nutrients and energy and return to normal functioning. On the contrary, in the case of intensification of autophagy processes, cells are destroyed, and in many cases their place is taken by connective tissue. Such disorders are one of the causes of heart failure.
Disturbances in the autophagy process can lead to inflammation if parts of dead cells are not removed.
Autophagy disorders play a particularly important (albeit not fully understood) role in the development of myopathies and neurodegenerative diseases. Thus, in Alzheimer's disease, in the processes of neurons in the affected areas of the brain, there is an accumulation of immature autophagosomes, which are not transported to the cell body and do not fuse with lysosomes. Mutant huntingtin and alpha-synuclein - proteins whose accumulation in neurons causes Huntington's disease and Parkinson's disease, respectively - are taken up and digested by chaperone-dependent autophagy, and activation of this process prevents the formation of their aggregates in neurons.

See also

Literature

  • Huang J, Klionsky D.J. Autophagy and human disease. Cell Cycle. 2007 Aug 1;6(15):1837-1849
  • Takahiro Shintani and Daniel J. Klionsky/Review/ Autophagy in Health and Disease: A Double-Edged Sword/Science, 2004, Vol. 306, no. 5698, pp. 990-995

Links


Wikimedia Foundation. 2010.

See what “Autophagy” is in other dictionaries:

    - (auto + Greek phagein is) the process of destruction of parts of cells or whole cells by lysosomes of data or other cells, for example. with involution of the uterus after childbirth... Large medical dictionary

    Diagram showing the cytoplasm, along with its components (or organelles), in a typical animal cell. Organelles: (1) Nucleolus (2) Nucleus (3) ... Wikipedia

    Lysosome (from the Greek λύσις dissolve and sōma body) is a cellular organelle with a size of 0.2–0.4 microns, one of the types of vesicles. These single-membrane organelles are part of the vacuome (endomembrane system of the cell). Different types of lysosomes can be considered as separate... ... Wikipedia

    - (from the Greek lýsis decay, decomposition and soma body) structures in the cells of animal and plant organisms containing enzymes (about 40) capable of breaking down (lysing) proteins, nucleic acids, polysaccharides, lipids (hence the name).... ... Great Soviet Encyclopedia

    - ... Wikipedia

    Andrea Solario. Madonna with a Green Cushion (circa 1507, Louvre). Breastfeeding, or natural feeding, is a form of nutrition for a newborn... Wikipedia

Finally, forget about juice cleanses or detox diets. That's not to say there's anything wrong with eating huge amounts of shredded kale. However, don't expect this to flush toxins out of your body any faster than if you were eating as usual.

Self-cannibalism

The good news is that there is a little-known way that you can actually cleanse your body, and it's a process you can control. All you need to do is practice self-cannibalism. Wait, what? No, you heard right! And yes, you can actually train your body to eat itself. Believe it or not, you definitely need it.

What is autophagy?

A natural process called autophagy (literally “self-eating”) is the body's built-in cleansing system. Your cells create membranes that hunt for the remains of dead, diseased, or worn-out cells, devour them, disassemble them for parts, and use usable molecules to produce energy.

Cleansing the body through recycling unnecessary particles

You can think of this system as your body's internal recycling program. Autophagy makes the human body more efficient as it gets rid of dead particles, stops the growth of cancer cells, and also prevents metabolic dysfunctions such as obesity or diabetes.

Benefits of Autophagy

There is also evidence that this process may play an important role in controlling inflammation and the immune system. When scientists bred rats that lacked the ability to autophagy, they became fat, lethargic, had high cholesterol levels and brain damage. When you put it all together, it's safe to say that autophagy is the key to slowing down the aging process, and you can learn how to control it in your body.

How to provoke autophagy?

So how should you eat yourself? This is a question you've probably never asked before, but now you'll know the answer. The first thing you should know is that autophagy is a stress response, so you have to put your body into a state of stress in order to ramp up your self-cannibalism systems. At the moment you think this article looks very strange, but believe me: if you read it to the end, your life can seriously change for the better. As is often the case, short-term discomfort can lead to long-term benefits, so you'll want to check out these three most effective ways to kick-start autophagy.

Exercises

You should always remember that exercise is the first way to bring your body into a stressful state. Exercising actually causes damage to your muscles, causing tiny micro-tears that your body immediately begins to heal, making your muscles stronger and more resistant to further such damage. Exercising is one of the most popular ways people inadvertently detoxify their bodies. So that feeling of freshness and renewal after a hard workout is a sign that you have cleansed yourself. One study took a closer look at autophagosomes, structures that form around damaged cells that the body has decided to get rid of. After scientists bred rats whose autophagosomes glowed bright green, they found that the rate at which these structures shed damaged cells increased significantly in rats that ran for thirty minutes on a wheel. And the speed continued to increase even when the rats had been running for almost an hour and a half without a break. But what about people? Determining the required amount of exercise and duration of exercise that will trigger autophagy, and the degree to which this process can be regulated, is a complex question that is not easily answered at present. However, it can be said that exercise has a lot of benefits even without its role in autophagy, so you should exercise anyway. And if you like heavy exercise, it's better for you. The more intense the exercise, the greater the benefits.

Starvation

The irony is that for those who like to “cleanse” the body with juices and smoothies, eating any food works against autophagy. Not eating is an action that will bring you a lot of stress. Your body definitely won't like it, but it will ultimately benefit greatly from it. Moreover, scientists have already demonstrated that intermittent fasting has many specific benefits, such as reducing the risk of diabetes or cardiovascular disease, all of which are attributed to autophagy.

It is also striking how much research has focused on the action of this process in the human brain during fasting. It is believed that this process may be an effective way to reduce the risk of neurodegenerative diseases such as Alzheimer's or Parkinson's disease. Some studies have found that intermittent fasting improves cognitive function, brain structure, and neuroplasticity, which may allow the brain to remember new information more easily. Of course, it has not been specifically proven that autophagy is the cause of this, and it is also worth mentioning that the tests were carried out on rodents. Therefore, we cannot immediately say with certainty that people will have the same reaction. Practitioners say that if you want to fast effectively, then you better do it periodically, in sessions of 12 to 36 hours. During fasting, it is recommended to limit physical activity to stretching or basic yoga.

Limit your carbohydrate intake

Although some professionals do not eat for 18 hours several times a week, they admit that it would be difficult for the average person to live this way. Simply avoiding food whenever possible can also be a good option - studies have shown that even one day of fasting a month can already reduce the risk of cardiovascular disease. But there's another way to get all the same benefits without giving up your favorite steak (though you'll still have to give up the candy). This method is called ketosis - an increasingly popular diet among bodybuilders and all those people who want to live longer. The essence of ketosis is to reduce your body's carbohydrate content so much that your body has no choice but to use fat as an energy source. Ketosis allows people to lose fat while maintaining muscle, and there is evidence that the diet helps the body fight cancer, reduces the risk of diabetes, and also protects against certain types of mental disorders, such as epilepsy. Research shows that more than half of children with epilepsy who followed this diet experienced half as many seizures. Ketosis is like bypassing autophagy. You get all the same metabolic changes and benefits as fasting, but without having to fast.

Autophagy is the process by which eukaryotic cells utilize their internal components by “digesting” them with lysosomal enzymes. It is a continuous process that maintains a balance between synthesis and degradation and provides the necessary conditions for normal cellular growth, development and death. In this article, we generalize the concept of autophagy to the general operating principle of living systems and propose the term protophagy to refer to prokaryotic processes like autophagy.

Autophagy (from the Greek αυτος - "self" and φαγειν - "There is": self-eating) is a cellular mechanism for recycling excess or damaged proteins, protein complexes and cellular organelles, carried out by lysosomes of the same cell. Such utilization performs several important functions, including obtaining nutrients during fasting, supporting cellular homeostasis and cellular immunity, carrying out apoptosis, etc. .

Typically the term autophagy used to describe intracellular processes. However, in a certain sense, it can also be considered as a general principle that works not only at the level of eukaryotic cells, but also in biosystems at other levels, such as an organism, a population, or even the biosphere as a whole. And at all levels of the organization of living things, many well-known processes can be correlated with the principle of autophagy, in particular, the regulation of the life activity of bacterial colonies. Here we will consider autophagy in a broader sense - as the process of a biological system absorbing its part to maintain its own structure and vital activity. Indeed: processes similar to autophagy appear on different “floors” of living matter ( cm. examples in table 1):

  • in eukaryotic cells (as communities of organelles);
  • in organisms (as communities of cells and tissues);
  • in ecosystems (as communities of living organisms), and finally;
  • throughout the biosphere (as a set of ecosystems).

For example, at the level of the body, one of the manifestations of autophagy is the metabolism of subcutaneous fat, when the body, during fasting, consumes its part (adipose tissue) with a redistribution of the released energy. Another example is apoptosis - the regulated “suicide” of cells necessary for the proper development of any plant or animal organism.

Autophagy is also present at the ecosystem level. Just as a eukaryotic cell constantly recycles old or defective organelles, in ecosystems some organisms are “consumed” and serve as a source of energy for others. This cycle of energy and matter in the biosphere is known under the term “trophic chains,” which can be defined as the constant redistribution of biological material within ecosystems.

The above examples are similar to autophagy in that they sacrifice part of the system to maintain the stability of the whole. Just as autophagy is required by the eukaryotic cell to maintain life during times of nutrient deprivation, the body's fat burning and ecosystem food chains are required to adapt to periodic energy shortages and stabilize energy metabolism.

Another fundamental function of processes like autophagy is the renewal of parts of the system in order to maintain its stability as a whole (homeostasis). The lifetime of any differentiated community is much longer than the lifetime of its individual parts - this is where a mechanism for maintaining stability is required. The stability of biosystems is achieved through constant renewal of components through autophagy. Continuous recycling of old components renews the biosystem and also allows you to replenish energy reserves. The same principle is used at other levels: in a eukaryotic cell, organelles that have spent their resources are digested by lysosomes, giving way to new ones. At the body level, damaged cells are eliminated by apoptosis or the immune system. In ecosystems, predator-prey relationships not only maintain the number of predatory species, but also regulate the homeostasis of the entire ecosystem, clearing it of weak and sick animals and protecting species from degeneration.

Autophagy is a common mechanism used at various levels of the biosphere. Almost every living system uses processes similar to autophagy for survival and self-regulation. Here we used the word "almost", since autophagy has not yet been described in prokaryotes. Taking into account the role of autophagy in all other biosystems, its absence in prokaryotes seems strange, to say the least. In this article we will try to show that prokaryotes are no exception, and they also have an analogue of autophagy, but it can only be detected if we consider prokaryotic communities not as single cells, but as multicellular “organisms”.

Prokaryotes as multicellular organisms

Today, enough data has been collected that in nature prokaryotes exist not in the form of isolated cells, but in the form of complex microbial communities. This bold idea was first put forward in the 80s of the twentieth century, and today it is supported by a solid experimental base. Natural colonies of prokaryotes have an analogue of endocrine signaling within the community (e.g. quorum sense), differentiation of cells into specialized subspecies, as well as complex patterns of collective behavior (joint hunting, collective digestion of prey, collective resistance to antibiotics, etc.). Autophagy, as a characteristic of differentiated communities, may well be another item on this list.

If a bacterial colony is a single biosystem, then its element will be a single bacterium. Similar to the eukaryotic organelle, the prokaryotic cell can be considered the simplest element of the bacterial community, surrounded by a membrane (and cell wall). This assumption leads to an interesting conclusion: autophagy should be looked for not inside the bacterial cell, but inside the bacterial colony. Indeed, “autophagic” processes are well known in prokaryotic colonies, although under other names - bacterial cannibalism, bacterial altruism, autolysis or programmed cell death. Bacterial cannibalism was first described as a bacterial colony's response to nutrient deprivation (see sidebar). The biological mechanism that triggers autophagy in this case is found in many species of bacteria - this is the so-called toxin-antitoxin system. Its essence is that during starvation, the colony lyses (“digests”) part of its cells so that the remaining bacteria receive enough food to survive. Thus, the colony experiences a lack of resources or external unfavorable conditions.

"Autophagy" in bacteria

Typical autophagic patterns have been described at the molecular level in many bacteria. For example, when there is a lack of food, some of the bacteria in the colony release a toxin into the environment. However, only some of them are capable of producing the molecule antitoxin- a protein that neutralizes the toxin when it enters the cell. Such cells survive and absorb the rest, killed and lysed by the toxin. This gives the survivors the energy needed for sporulation. Similar processes have been found in many species of bacteria.

For ease of description we will introduce the term protophagy as a collective synonym for the processes of bacterial cannibalism, altruism, autolysis and programmed cell death. The prokaryotic community is an integral biosystem that, if necessary, processes part of itself to maintain stability. In protophagy, the autophagosome (membrane vesicle with degradation products) is the prokaryotic cell itself. Protophagy is in many ways similar to autophagy in eukaryotes (Fig. 1):

  • both processes operate on similarly sized “vesicles” (the size of a bacterium is approximately equal to the size of a mitochondrion or peroxisome);
  • both pro- and autophagy are activated by similar signals (fasting or stress);
  • both processes are carried out according to the same principle (regulated consumption of its part by the biosystem);
  • both processes serve a common goal (the survival of the biosystem under stress and maintaining its homeostasis).

Figure 1. Fundamental similarity between protophagy and autophagy.

Like eukaryotic autophagy, protophagy is used for more than just food production. For example, protophagy serves pathogenic bacteria to invade the host organism (Fig. 2). It is known that the host microflora (symbionts) can effectively inhibit the growth of pathogenic microorganisms. In order to suppress competition, some pathogenic bacteria activate the antibacterial immune response of the host organism through protophagy. To do this, part of the pathogenic population inductively self-lyses, releasing toxins, which causes local inflammation. As a result, the body's immune system destroys most at This is part of the symbiont bacteria, while pathogenic bacteria avoid detection and, after the end of the inflammatory reaction, multiply unhindered in the host tissues. Interestingly, in the absence of symbiont microflora (for example, during experimental infection of special lines of sterile mice), such pathogenic bacteria colonize the intestine without inducing inflammation. This suggests that protophagy here is a specific survival mechanism of pathogenic organisms, which is activated only under unfavorable conditions.

Figure 2. Similar roles of protophagy and autophagy in the activation of the immune response.

What does the concept of protophagy give us?

The introduced concept of protophagy is interesting not only as a bare theory, but can also be useful in practice. For example, bacteria are widely used in biotechnology today, and manipulation of protophagy processes may provide a way to maintain bacterial culture stability on an industrial scale. Thus, protophagy activators should improve the quality of crops by activating natural mechanisms for eliminating weakened and damaged microorganisms.

Another important area of ​​application of protophagy may be medicine. Today, bacterial resistance to antibiotics is one of the key pharmacological problems. Instead of killing individual bacterial cells (as is done today with antibiotics), we can concentrate on disrupting bacterial communities as a whole. Such methods are already being developed - these are, for example, blockers of bacterial “quorum sensing”, which are aimed specifically at disrupting intercellular signaling in bacterial colonies in order to make them vulnerable to the human immune system. And although this topic is just developing, and there are still more questions than answers, the general vector of work shows that disruption of communication between individual bacteria has every chance of becoming the therapy of tomorrow. In this context, protophagy activators will help to destroy the protective barriers of the bacterial colony and make it vulnerable to the host immune system.

Afterword

The main question that may arise after reading this article is whether it is necessary to introduce a new term - protophagy- to describe well-known facts? In our opinion, expanding the concept of autophagy and introducing the term “protophagy” is necessary and useful.

The biosphere in a certain sense resembles a fractal, where each subsequent level repeats the previous one. Similar processes are similar to each other not only externally - they all have similar causes and principles of regulation. The concept of protophagy, which unites disparate processes of prokaryotes together, allows us to generalize and better understand the deep mechanisms that regulate the life of prokaryotic colonies. This provides undeniable benefits for the biotechnology and medicine of tomorrow.

Whether the term “protophagy” will catch on and whether other scientists will find it useful, time will tell. We outlined what we thought was important in an article published in the magazine Autophagy. If microbiologists accept these generalizations and find them useful, we will be very pleased. If the citation rate of our article does not break records, it means that we have fallen into medieval scholasticism and overestimated the significance of our own inventions. In any case, it was worth presenting this work to the esteemed public - after all, protophagy is a special case of autophagy in the bacterial world and follows the same laws as its other manifestations - be it autophagy in a eukaryotic cell, trophic chains in the biosphere, or fasting according to the fashionable method before the beach season, which, by the way, is already around the corner.

Based on an original essay in Autophagy .

Literature

  1. Daniel J. Klionsky, Fabio C. Abdalla, Hagai Abeliovich, Robert T. Abraham, Abraham Acevedo-Arozena, et. al.. (2012). Guidelines for the use and interpretation of assays for monitoring autophagy. ";
  2. K. Lewis. (2000). Programmed Death in Bacteria. Microbiology and Molecular Biology Reviews. 64 , 503-514;
  3. Bärbel Stecher, Riccardo Robbiani, Alan W Walker, Astrid M Westendorf, Manja Barthel, et. al.. (2007). Salmonella enterica Serovar Typhimurium Exploits Inflammation to Compete with the Intestinal Microbiota. PLoS Biol. 5 , e244;
  4. Morten Hentzer, Michael Givskov. (2003). Pharmacological inhibition of quorum sensing for the treatment of chronic bacterial infections. J. Clin. Invest.. 112 , 1300-1307;
  5. Markina N. (2010). "Biologists have learned to command bacteria." INFOX.ru;
  6. Petro Starokadomskyy, Kostyantyn V. Dmytruk. (2013). A bird’s-eye view of autophagy. Autophagy. 9 , 1121-1126.