Interview with a bioenergetic

How Vladimir Skulachev proved and disproved Peter Mitchell by Discovering Mitochondrial electricity

Alexey Torgashev, PCR.news

Vladimir Skulachev is one of the founders of the science of bioenergy. That is, the field of biology, which studies how ATP is produced in organisms — the main energy currency of cells. Skulachev, a world—renowned scientist, tells the story of a series of his works of the 60-70 years of the XX century about the discovery of mitochondrial electricity. The interview mentions names familiar to every biochemist on the planet, but a special place is given to Peter Mitchell, the creator of the chemiosmotic theory, for which he received the Nobel Prize in 1978. Vladimir Skulachev, according to many, should have shared this award with Mitchell, and we also ask the question "why not?" in an interview.

Let's start with definitions — otherwise we will not understand the importance of the historical events that our interlocutor tells us about. Those who need more details will find them in the book Principles of Bioenergetics (Springer-Verlag Berlin Heidelberg 2013).

Cellular or tissue respiration is not the same as what is called breathing in everyday life. This is a chain of biochemical reactions in the cells of living organisms, during which carbohydrates, lipids and amino acids are oxidized to carbon dioxide and water, and energy is stored in the form of macroergic compounds (ATP molecules).

The stages of cellular respiration are glycolysis (if it goes without oxygen, it is called fermentation), pyruvate oxidation, tricarboxylic acid cycle (Krebs cycle), oxidative phosphorylation. The topic of our conversation is the last and most difficult stage. Like all stages, except glycolysis, it occurs in the mitochondria. When nutrients are oxidized, carbon dioxide and protons (H⁺) are formed, which are pumped from the inner space of the mitochondria into the space between its inner and outer membranes through special channels. As a result, the membrane is charged like a capacitor: on its outer side "+", on the inner "–". Then, moving back under the influence of this potential difference, protons pass through a channel in the rotary ATP synthase - a protein complex shaped like the fruit body of a mushroom, the "leg" of which penetrates the membrane, and the "cap" sticks out into the matrix of the mitochondria. Individual parts of this complex are mobile. When an ionic electric current passes through the ATP synthase, the electric field "rotates the turbine" - the mobile part of the ATP synthase. Due to rotation, ATP synthase produces ATP from ADP and phosphate. The spent electrons and protons are absorbed by oxygen, forming a water molecule. When a stream of protons flows past the turbine, the energy is dissipated as heat. And this is not necessarily a bad thing: warm-blooded people need to maintain body temperature.

For now, let's remember that the main events of the "gorenje" of nutrient substrates and energy synthesis inside a living cell occur on the membrane and between the membranes of mitochondria.

— We discovered mitochondrial electricity in the 60s of the last century, — says Vladimir Petrovich. — Before our research, it was believed that electricity occurs in living beings only in one place — on the membrane surrounding the cell: there is a difference in electrical potentials between the inside of the cell and the outside of the cell. This idea dates back to the XVIII century. And indeed, there are electricity generators in living beings, they sit in this outer cell membrane and charge the inside of the membrane more negatively than the external environment. And a bold dot was put on this: if there was some kind of a section in the textbook about electricity in living beings, then there was a paragraph or two.

But even before your work, there were works on neurons, electricity in the nervous system?Yes, it would seem that this has greatly advanced science, because everyone has taken up neurons.

But this is a special case, the outer shell of neurons is the very outer shell of the cell. And the dogma that everything ends on the outer membrane of the cell did not go further. It seemed that biophysics had exhausted itself and, although electricity is a colossal branch in physics, it was believed that for some reason evolution could not come up with anything in living cells. It turned out that this is absolutely wrong. It turned out that there are up to 25 thousand mitochondria in the same cell, and each mitochondria contains a thousand small thermal power plants and generates a huge amount of electricity, completely incommensurable with that which the biologists who studied the outer membrane were engaged in.

How did the paradigm shift happen? It's not just the work of your group.The discovery is absolutely anecdotal.

Firstly, it is based on the erroneous assumption of the brilliant biologist of the second half of the XX century, Peter Mitchell, that there is, as he called it, a chemiosmotic machine in mitochondria.

The famous chemiosmotic hypothesis…Yes, yes, chemiosmotic.

And osmosis is a gradient on the membrane. Ionic, nonionic — it doesn't matter. If there is pure water on both sides of the membrane, then there is no osmosis, and if there is something in this water on one side, then the more of this, the more osmosis will be. Biologists before Mitchell had very little to do with this phenomenon. And partly by this name he wanted to emphasize that he was invading some very unusual field of biology.

Who is Mitchell? An English biologist, he started as a demonstrator with a professor at Cambridge, and became engaged in real science when he began teaching bacterial biology himself. And this is the first thing that pushed him against the membrane. How he got into bioenergetics is a completely incomprehensible thing, because everything he researched before 1960 was all sorts of circumstances that evolution came up with in order to drag something into the cage, what it needs and what it doesn't need, to throw it out as soon as possible. It's also beautiful, but he couldn't give birth to any ideas. And the first and last idea that he gave birth to blew up, in the end, this area. Mitchell was just God. "In the beginning was the word," he said the word.

His hypothesis was wrong, but... I must say that I adored him. In bioenergy, Mitchell was called president, and I was called Prime Minister.

Peter Mitchell and Vladimir Skulachev

As far as I understand, Mitchell wasn't going to do electricity at all, he wanted to figure out where the ATP in the cell comes from. Is it possible to briefly formulate the essence of his hypothesis, which was published in 1961?The point is to find out how ATP molecules are produced in cells when burning nutrients.

ATP is, I would say, a biological currency. It is paid inside the cell for any processes that require energy. And to get this currency, you can use different ways.

There is a way of glycolysis, alcoholic fermentation, which at that time had already been investigated, but it was clear to everyone that these are additional bioenergetic components, the main ones in very few living beings. And in most cells, if there is oxygen, it is used to burn nutrients in the mitochondria and produce ATP due to this energy, which is released during combustion. This is the process of breathing.

If we continue the analogy with currency, then glycolysis is clearly a secondary method of its extraction. You can build a house and get paid for it, or you can sweep the street and also get paid, but less. Here is glycolysis — these are wipers. And mitochondria with respiration are skilled workers.

At the time of the appearance of the Mitchell hypothesis, the Krebs cycle was already known. That is, all the preparatory stages for cellular respiration. And it was known that respiration takes place in the mitochondria, right? And Krebs was alive, and Leninger, other leading biochemists. And what did you need to find out? What did the biochemists say then? What were the ideas?It was said that this mysterious process is respiratory oxidative phosphorylation.

Who is about to receive his Nobel Prize. Everyone was waiting for the only protein that makes ATP when the products of the Krebs cycle are oxidized with oxygen to be finally cleaned. They said: "Everything is there! Everything is there! The Krebs cycle, all variants, oxygen, have already found a cytochrome oxidase that seizes it… And we need to find that single enzyme as soon as possible! Everything is absolutely obvious!" (Hans Krebs — Nobel laureate in physiology or medicine in 1953 "For the discovery of the citric acid cycle"; Albert Leninger — biochemist who showed in the late 1940s that mitochondria synthesize ATP due to the work of the electron transport chain, author of the most famous textbook on biochemistry. - A.T.)

Just dripped different mixtures into a test tube and saw what would happen?Yes, yes.

There were two monstrous scandals when researchers claimed that they had found this protein. In one case it was a graduate student, and in another case it was the deputy head of the laboratory, a very famous person.

David Green?Yes, but he had nothing to do with it.

He was great, he discovered four complexes — components of the respiratory chain. He was repeatedly nominated for the Nobel Prize. And that scoundrel, his deputy, just came up with everything and drew the results. I heard him speak at the World Congress in New York.

And Ephraim Rucker exposed him. And this is just the second scandal. Rucker participated in the experiments of his graduate student named Spector. He manipulated more cunningly. Do you know what he was doing? He needed ATP to be synthesized. And now he seems to have discovered and isolated a protein that does this. It was very simple to find out: there is always a scatter of data in experiments, so this graduate student took data where ATP synthesis randomly — because of "dirt" - went up, and threw away the data where it went down. And he turned out to have a colossal authenticity, because he drew everything with his own hands, you know? And the blow after the exposure was stronger, this issue was considered by the United States Congress. Rucker himself was an amazingly sweet and talented person, one of the most famous bioenergetics, he discovered a lot of things.

In general, everyone was looking for a pure enzyme that can make ATP without any mitochondria. Mitochondria were in the way at all, why are they, why are there two membranes? And Mitchell said enough of these stories, we don't need a third one. You are looking for something that no one has lost, there is no such protein.

(David Green is a biochemist who described the main components of the electron transport chain of mitochondria in the 70s of the last century; Efraim Rucker (Reker) is a biochemist who discovered ATP synthase in 1960. — A.T.).

Did he directly postulate?Yes, he postulated that there is a completely different thing.

From chemistry... This was also inaccurate… This whole story about the dead is terrible… I am the first to tell you, I have been silent for many years and have not described it anywhere. Mitchell's terrible mistake… In fact, this is also wrong. If Columbus did not discover India, but America, what is he, not Columbus now?

So what did he formulate, besides the fact that it's not protein?So this is the most important thing: aerobic respiration has nothing to do with how glycolysis and fermentation work.

And we're all looking for proteins, and that's why we haven't moved a step in so many years. It was an immaculate postulate. But as soon as he tried to print it, refusals went everywhere. Moreover, there were great people on the list of losers, and he had no experiments, except for the fact that no one had found anything for half a century.

And then he formulated the chemiosmotic hypothesis. This is the first thing that was printed on him, and immediately in Nature. In short, everything is very simple: the synthesis of ATP during glycolysis and fermentation is one chemistry turns into another chemistry. One chemistry: there was glucose, and now it's not glucose, now it's lactic acid. And the second chemistry: this is ADP and phosphate combine and ATP is obtained. Due to the energy that was released from glucose when lactic acid was made from it. So, there is no such thing when breathing, he said. And what is there? But what — why he came up with it, I don't understand at all — and that was his mistake: that there was chemistry, and then there was osmotics. (To be honest, osmotics is also chemistry, quite different, of course.) This could work, especially since he very wittily said: well, what is osmotic? It's a little water, a lot of everything else. And what is ATP synthesis? It was phosphate, it was ADP, they bit off a piece of phosphate, bit off a piece of ADP and connected both parts. And what happened, besides ATP? He said: guys, the problem is that another water molecule has turned out, and this is osmotic. The more you pour there, the less osmotic. By the way, Mitchell immediately came up with why the membrane was needed. He put a lot of things together in parts. And there was nothing wrong with his energy. Energy appears due to the movement of water through the mitochondrial membrane.

He said cunningly: if it's just water in water, then nothing will work, and everything happens in a membrane in which there is no water. The membrane is greasy, there is no water and there was no water. And then ADP and phosphate came, ATP and water were formed where there was no water! With all the ensuing energy circumstances.

That's where the word "osmotic" came from. Who closed his scheme? Rucker. Even before Rucker was disgraced by the US Congress.

I see. According to Mitchell's initial hypothesis, the water molecule does not appear ON the membrane, but in the THICKNESS of the membrane, where it does not belong, it is thrown out of there like a drop from sunflower oil, and thanks to this energy arises. This was the original version of the chemiosmotic hypothesis, and not what we now call it — pumping out ions, then the reverse movement of ions, torsion of ATP synthase, synthesis of ATP. And what was Rucker's discovery?He discovered that ATP is formed not in the membrane, but in special outgrowths from the membrane that stick out into the mitochondria, and there is solid water.

And the question hangs: how, why is oxygen needed at all, and how does it give its energy to make ATP? Again, nothing adds up, you know? It turned out that Mitchell had come up with something that would lead us nowhere again. Previously, at least we were waiting for someone great to finally find this protein, throw the membrane, mitochondria to hell, and then on this pure protein from ADP-phosphate, during the oxidation of some of the substrates of the Krebs cycle, get ATP! And when Rucker showed that ATP is not made where Mitchell thought, but on these very mushroom-like outgrowths, it brought down the whole hypothesis.

Outgrowths, is this probably what we know as ATP synthase?Yes.

The question itself came from the Mitchell hypothesis, but it turned out that Mitchell was wrong. And who is right? Unclear. And then the electricity came.

Your job?Our job, that's right.

Efim Lieberman and I did... This table was usually covered with different pictures. The whole technical part of the experiments, it was all here. Lieberman came up like that, walked around the table: no, Volodya, I can't do that, and left. It was too difficult for him. He demanded some great ideas immediately and today. He was a physicist, worked at the Institute of Biophysics in Pushchino.

It was we who showed in the first experiments that oxidative phosphorylation is biophysics, not biochemistry. This is the most ordinary thermal power plant. Which accumulates ATP by kilograms per day in our bodies.

Therefore, a membrane is needed to make physics out of chemistry. Coal in power plants is chemistry, and electricity is physics. It's the same here: all the food that mitochondria eat, it burns! And a healthy electric field is obtained. And why does it work? Because it burns right in the middle of this membrane, not somewhere there like a Rucker, but in the middle of the membrane. But it's very dangerous, so you can set yourself on fire. So that this never happens, there is a lot of water around, and all the oxidation energy produces an electric field. Two hundred millivolts per thin membrane — if you recalculate the size of power plants, it would be kilovolts. And all the electricity is directed to the same place: to make ATP on the cap of ATP synthase by rotating this cap.

Is that why ATP synthase is called rotary?Yes. Electricity causes the rotation of this mushroom cap.

And when it rotates, this rotation is again used for chemistry. That is, first gorenje — chemistry, at the end synthesis of ATP — chemistry, and in the middle electricity: without this machine is absolutely helpless. And these experiments, which showed the electrical nature of the process, were set up by us, Rucker and several other people. And Mitchell was still talking: "This is a chemiosmotic concept." - "And where is osmosis, I ask you?" He replied: "Well, you know, Vladi (he called me Vladi), not everything in the world is arranged in such a way that it can be explained. God did something." I say, "Do you believe in God, the bearded old man?" "Why should I believe in this idiocy?" was his answer. That's what we had.

Are the experiments you are talking about experiments with the separation of ATP synthesis and respiration? I've read about them in books.No, no.

We started with disconnectors, but this is just a historical thing. (Disconnectors are substances with which you can disconnect two processes in mitochondria — the actual burning of nutrients and the synthesis of ATP. In this case, all the energy goes into heat, this happens, for example, when the body is cooled. The action of disconnectors is based on zeroing the difference of electrical potentials on the membrane. The disconnectors can be a variety of molecules capable of dragging ions through the membrane. — A.T.). And the proof of electricity was made without disconnectors. Lieberman and I came up with the experiment, and this was the greatness of Lieberman, because he was a physicist, and he scolded me in every possible way that I didn't know physics well. We have proved an electric field in the inner membrane of the mitochondria.

In what way?It's very simple: we showed that all the pluses — positive ions — went inside the mitochondria, and all the minuses, regardless of their device, came out of it.

Ions, I must say, as a rule, do not penetrate through the membrane, but we knew how to make penetrating ones. This is the proof of membrane electricity! What is electricity? This is the potential difference between two points. And we have shown that the outside of the mitochondria is a plus, and the inside is a minus.

We made liposomes — this is not a mitochondria, but a membrane ball without a single protein. And it had the same properties: if we included a single enzyme from the mitochondrial complex in this bubble, then this electric field immediately appeared. So we did it first with cytochrome oxidase, then with another enzyme, with a third...

That is, each of these enzymes created a field. And this field disappeared if a disconnector was given.

In the same year, Albert Leninger, the well-known bioenergeticist and author of the most famous textbook on biochemistry, already mentioned by us, put an experiment on the action of the disconnector dinitrophenol on an artificial membrane. It was a so—called black phospholipid membrane (black means so thin, less than the wavelength of visible light, that it no longer refracts light rays). The membrane covered a small hole in the Teflon partition separating the cuvette with the solution into two compartments. An electrode is immersed in each of the compartments, with a voltmeter between them. In this simple system, it is easy to measure the resistance of the black membrane. So it turned out that the addition of dinitrophenol in both compartments of the cuvette or even in one of them significantly reduces the resistance of the membrane. Because dinitrophenol drags hydrogen ions through the membrane.

And what does this have to do with measuring the potential on the membranes of liposomes and mitochondria?Lieberman figured out how to measure.

Mitochondria just float in the cell compartment, which is separated from the other compartment by a black membrane. And you need a substrate to start breathing. If breathing has started, a potential arises, and we see how ions pass from one volume to another through the black membrane. Well, the same Skulachev-ion, SkQ, for example. And you can measure how much it was before some substrate was added, and after. And there is Nernst's law, by which we calculated the absolute value of electricity on the membranes. And exactly the kind that ATP can still do.

Mitochondria in one cell, nothing in the other, a black membrane between them. mitochondria change the ion content in the solution in their half, and a potential arises between the two cuvettes? The same acidification, the mitochondria throws these protons completely outside, behind the outer membrane, and does not accumulate between the membranes? Is that right?True, but the outer membrane of mitochondria is always leaky and does not prevent protons from escaping.

 But I can't get through to the funniest part. The funny thing is that there is electricity in the 1961 work for which Mitchell received the Nobel. Not only is it there, it is directly calculated what it is. Who did this? Mitchell's younger brother, a physicist. Mitchell didn't understand this, but he really liked that now there is some kind of mathematics, inserted it into the article.

And now five years have passed since 1961, when there was a monstrous failure of Mitchellianism. It was in Warsaw, at a conference of biochemists in Europe.

Have you been there?I was there, I met him there, it's 1966.

They decided to give Mitchell the floor and made him chairman of the meeting. He looked at the list, and there are all these old-regime people who have been unable to do anything for fifty years. He didn't give his word to anyone. Nobody! And he talked for two hours alone.

And in the hall on the first row sat Britton Chance, the famous biophysicist, bioenergetic from Philadelphia. And he said, "Dr. Mitchell, what happens if you add calcium to the mitochondria?" Mitchell looked at him like a soldier at a louse: "Nothing will happen, calcium has nothing to do with it." - "Can I just show you one slide?". "Well, if you insist." "Yes, I insist." Showed this slide. And there is an experiment in which ADP is not added specifically to the mitochondria. In this case, they can't make ATP, but you can make them breathe. How? Add a disconnector. They do not make ATP, but heat is obtained. Here we call breathing the production of thermal energy from substrates. And this cunning Chance gave calcium instead of a disconnector. And Mitchell saw with his own eyes that when calcium was added, breathing suddenly appeared. Although he understood that calcium can't make ATP! And he said: "I don't understand, I don't understand!" He collected the papers and left. And Chance stood with his chest forward—a young Olympic champion in yachts, his chest is so wide—looked at everyone and said, "Well, that's the end of the Mitchell hypothesis." And then people started to get up, I will never forget it, and this is Poland, 1966, the state has quite a little money, the congress was held at some school. And the chairs there, as you get up, they slap loudly: bang, bang!

How did it end?Mitchell came to his home in Bodmin, in the south of England, where he had his own laboratory, and immediately called his physicist brother from London: "Come, I've been disgraced here."

It is amazing that after all, in the work of 1961 there was this electricity, which his brother pointed out. And Peter not only did not take him as a co-author, he did not even mention who this formula belongs to. It's quite simple, of course, so it's not some kind of discovery, but if there is a proton movement, then it describes one hundred percent the size of electric potentials. He just didn't understand the meaning of it.

In Bodmin, he and his brother reproduced Chance's experiment and made sure that he was right. Then it would turn out that calcium somehow promotes breathing. Then Mitchell said, "Now I'm going to add potassium. So what? Nothing will happen, potassium does not pass through this membrane. No, I'll add valinomycin." (Valinomycin studied Ovchinnikov, he showed that valinomycin carries potassium through the membrane.) And it turned out that if potassium is given with valinomycin, it will be the same as with calcium. Mitchell guessed that there was already a natural calcium carrier in the membrane. And potassium needs an artificial carrier — valinomycin.

And what about calcium actually?Little was known about calcium then, but now it is clear that there is a special protein-a calcium carrier.

It was discovered in the XXI century.

Why is the calcium story so important?Both calcium and potassium are cations, positively charged ions.

If, for example, the enzymatic transport of ions across the membrane was important for the synthesis of ATP, then the chemiosmotic hypothesis would be correct in the original sense. But in the end it turned out that it is the potential difference on the membrane that is important, it is its energy that is spent on the production of ATP. There is a potential difference, that is, electricity, an electric current arises in the channels of ATP synthase, as a result, ATP synthase rotates, and produces ATP for each turn, there is no electricity - it does not rotate. And electricity itself produces oxidative phosphorylation in the mitochondrial membrane due to the transfer of electrons to the enzyme chains from the substrate.

And then a situation arose when Rucker, and he was a supporter of Mitchell, proved that water, which could create some kind of osmosis of the inner membrane, does not create it. And then Mitchell realized that the name of the hypothesis was wrong. And for the wrong name, he would not have received the Nobel Prize. He had a dream of becoming a Nobel laureate. On the other hand, there is a rule of life: if you are a father, you can call your son whatever you want. Trying to get away from electricity — it cost science a lot, because a lot of people have been doing nothing for many years.

How did it turn out to prove the hypothesis?You know, people believed in it already in 1969.

I will never forget my most successful performance. I spoke at the World Biochemical Congress in Madrid for an hour without a piece of paper, although I was given seven minutes at first. Because there was already the first article in Nature, quite short. And clumsily written, of course. And they changed the name! We wrote "Disconnection of oxidative phosphorylation and membrane potential", and the reviewer corrected it to "Conjugation". How I got to the Congress is a separate story. At that time, it was impossible to go twice a year. And this is done in the most beautiful places, and I didn't care, I just needed to hear the discussion, see Chance. He called me Volodgio. Mitchell called Vladi, and he called Volodzio.

I told you about penetrating ions. They have not yet been called Skulachev ions, it was Green who later called them Skulachev ions. And when I finished, someone jumped up and shouted, "Mitchell is proven! Mitchell is proven!" and a sea of hands. And no one spoke after me anymore, because so many people rushed to the podium. The Chairman could not do anything — this is a fantastic, indeed, success.

Why do you think you didn't get the Nobel Prize?You know, it's a big secret.

I knew a member of the chemistry committee — after all, Mitchell got a degree in chemistry — Lars Ernster, he was a very good friend of mine, and then, a year later, at the next congress, he takes me by the button like this: "Vladi, Vladi, how is it, Vladi?". I say, "What's the matter?" He says, "Nobel Prize!". I realized that I was very close.

Could share…Of course they could.

But Mitchell got one. And I think I should have gotten both Rucker and Lieberman for sure.

Was Lieberman still alive in 1978?Yes.

And in Russia. He then left for Israel. Do you know what he has been doing in recent years? He was trying to prove that the Torah is some kind of text, like DNA. Lieberman was a wonderful man. He fought as a pilot, flew once on one wing when he was shot down...

You have nothing to be offended about anyway. So many first-class works. I only counted five or six in Nature in ten years in the seventies.It was an amazing feeling.

We followed terribly simple paths. We went forward, and it turned out that photosynthesis works the same way, both in green plants and in cyanobacteria. The same way those strange bacteria are arranged, which have no Krebs cycle at all, but there is only one stage. And no more is needed, it's enough to eat something. There is no cytochrome oxidase, but there is another enzyme that absorbs light… Or is that how bacteria move? There was the first American work that indirectly showed that, it seems, if there is no potential, then the movement is slowed down. And we, who were already firmly convinced that this was an electric motor, and not anything else, - we dropped the potential from the bacteria, and the motor jammed. The movement of bacteria has completely stopped.

Or another example of how electricity is transmitted in a cell? Mitochondria can be very long, and I kept thinking, maybe it's an electric cable? After all, dragging ATP from one place to another can be very energy-consuming. And it's easy to transfer electricity. And we checked it elementary: we irradiated this mitochondria with powerful light at one point and predicted that if it was one cable, then the whole cable would go out. They made a dye. And that's exactly what happened. If oxidative phosphorylation takes place in one place, then the potential is transmitted along the entire length of the mitochondrial cable.

Skulachev's ions also appeared in the course of this work, didn't they?The Skulachev ions are a very funny story, because they didn't take root at first.

Only one magazine had a review of Green. He called one of the chapters in the review that way. He glorified me as an author, an affectionate word and a cat is nice. And then this whole program was taken by Michael Murphy in Cambridge, in the late 90s. He decided to make a medicine out of Skulachev ions. An antioxidant. And he took the wrong one. All quinones are antioxidants, but if you overdose, quinone always becomes a pro-oxidant from an antioxidant. It's very dangerous. And if you want to make a medicine, then you must definitely have a "window" between "anti" and "pro". And our first experiments were also on the same substance. It is available in pharmacies in Russia and other countries.

Anti-aging creams are added.Murphy invited me to his seminar, and I saw his experiments.

I said, "Michael, you know, the window is only one and a half times. Your ion is not suitable for this at all." And ours, if measured in different ways, from 30 times to 3000 times from an antioxidant to a pro-oxidant.

When we already began to deal with these ions against aging, then I remembered that it was called the Skulachev ion in Green's article. And then my consultant in the USA just rejoiced. That's it, he says, no court of Murphy against Skulachev will win, since the case is about Skulachev-ion. So Skulachev is ion.

Do you take it orally yourself? And how?I have never been to a doctor in these ten years, except for one terrible case, you will not wish your worst enemy.

My daughter was treated by a man from Tibet, and he gave me some balloons. I caught a cold once, she brought these balls, I needed one ball in the morning, another in the evening. And in the morning I forgot, and in the afternoon I remembered. And instead of there being a gap between the two balls about half a day, it turned out to be only three or four hours. I went to bed and felt like I was dying. It's just impossible to breathe. An ambulance arrived and took me to the intensive care unit. I was there for a day and a half. It was the only "fatal" case in my entire long life.

But you look, I must say, very good. Are you 86 already?I turned eighty-seven in February.

And you work all day long…I'll die if I don't work.

I don't know how not to work. I also watch football. The only thing that attracts me in life besides science is Dynamo Moscow. I've been rooting for him since I was nine...

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