Mitochondria

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Life on our planet began about four billion years ago. And about a half of that time there were no any mitochondria. All forms of life were represented only by bacteria and archaea (these are very similar to bacteria, though have important distinctions that were noticed quite recently, while earlier they were thought to be variations of bacteria). And also there were viruses, about which there is still no consensus, whether they are a form of life or biological nano-machines. Viruses do not even have cells. They have a membrane, inside which their genetic code is stored, and a mechanism of attacking living cells in the form of protein molecules on the surface of the membrane. 

Cells of bacteria and archaea are rather simple. There is an external membrane filled with a liquid, in which everything these single-celled organisms need for their lives is dissolved,  including their genetic codes. They do not have a separate nucleus and separate organelles with their own membranes separating them from the rest of the bacterium or archaeon.  Such simple organisms are called prokaryotes. They are so simple that they cannot form multicellular organisms, even though they may form colonies with a kind of "social life" in them, though, rather simple one. 

Bacteria, archaea and viruses exist now. But, about 2.5 billion years ago (some scientists believe that much later, 2 or even 1.5 billion years ago) a revolution occurred that opened new ways of development of life and led, among other things, to appearance of multicellular organisms: plants, animals, mushrooms and, eventually, us, humans.

The revolution consisted in that that some small bacteria settled inside larger bacteria or archaea. How and why it happened, is not known. Maybe, the larger bacteria swallowed the smaller ones, but were unable to digest them. Maybe, the smaller bacteria invaded the larger ones with the purpose of robbery or parasitizing. Or, maybe, both, willingly and without enforcement, decided to live together and cooperate for survival. 

After that union (or invasion, or appropriation), the smaller bacteria delegated all the troubles of fining food to the larger bacteria. Having no need to seek food, they simplified. But they developed an ability that the larger bacteria lacked – they became very efficient at charging ATP molecules both for themselves and for the larger bacteria. As a result, a symbiosis formed, a cooperation between different living creatures. When we found these small simplified bacteria inside cells of animals and plants, we called them "mitochondria". Such cells with mitochondria further developed, and acquired a separated nucleus and various organelles. We call all creatures with such cells, whether they are single-celled or consist of hundreds of billions of cells, eukaryotes. 

Of course, this revolution could not have occurred and did not make any sense in the first 1.5 to 2 billion years of life on Earth. Initially, in the atmosphere of Earth, there was no free oxygen, and we know that mitochondria need oxygen for obtaining energy and charging ATP molecules. Initially, bacteria and archaea relied upon chemical reactions with available inorganic substances, as a source of energy. Later, when they accumulated a considerable biomass, some of them switched to obtaining energy by fermentation. Later, some of them found a way to use the solar energy for thier biological process – these were the first cyanobacteria (named by their color, which is light-blue with a tint of green – the cyan color). With the help of solar energy, they began to produce glucose and fructose out of carbon dioxide, which was abundant in the atmosphere of that time. This was the early photosynthesis. And its byproduct was free oxygen. Eventually, the amount of free oxygein in the atmosphere became so large, that a considerable part of bacteria were poisoned by it (because they were not adapted to it). And those that survived, obtained a possibility to use oxygen for acceleration of their biochemical reactions. Some bacteria still cannot live and reproduce in presence of oxygen (anaerobic bacteria). Later, this oxygen, which once almost killed life on Earth, became a precondition of the biological revolution described above, that lead to appearance of mitochondria, complex (eukaryotic) cells, multicellular organisms and, eventually, us.

Some cyanobacteria did a similar trick – settled in single-celled organisms that already had mitochondria and began to specialize on conversion of the solar energy into chemical energy in the form of fuel for mitochondria. We also do not know if this was a free union, or forced appropriation, or invasion. But the result was the beginning of development of algae and all plants.

Living creatures that use sexual reproduction for continuation of their species (and these are far from being all creatures),  transfer their genetic code to their descendants – a half from the mother, and a half from the father. This ensures genetic variability that is necessary for survival of the species. But fathers give only the genetic code of their nuclei – spermatozoan of animals or pollen of plants do not have mitochondria. And the egg cell has mitochondria from the mother. This genetic code is not absolutely stable. Mutations occur to it, as they do to the genetic code of the nucleus. This is why the genetic codes of mitochondria of different species are different. And within one species they are different in different individuals. And, after many generations, they become different in the descendants from the same female. But still they have some signs of those very first mitochondria, which used to be separate creatures. 

Though mitochondria have simplified considerably and cannot live separately from those cells, in which they once decided to dwell, they still have quite a lot of autonomy. Yes, they strictly perform their obligations (taken voluntarily or imposed on them) as for charging ATP molecules with energy. And they do this, because, without this, the cell will die, and they will die with it. But beyond this obligation, they are rather free. They reproduce by division (like bacteria), they unite, they live, and they die. Even in charging ATP with energy, they have some degree of freedom – they can charge or not charge (but not to the extent, which can cause the death of the cell). And all this independently from the cell, in which they live.

Well, not entirely independently. Perhaps, they would like to reproduce more frequently (not above a certain number of them per cell, depending on the kind of cell), but the life of the cell can be unfavorable,  and then mitochondria also suffer – their population on the cell reduces, and the load of producing energy increases for each of those that are left. This may continue until remaining mitochondria cannot cope with producing enough energy, and then the cell dies. Or the cell may get broken and start obtaining energy exclusively by fermentation, having become an enemy to the organism, in which it lives. 

We can imagine a mitochondrion as a small electric power plant that burns fuel to rotate the generator and produce electricity. 

Of course, mitochondria do not have a furnace, and "burning" occurs more calmly, without a flame. But in this process, the fuel is oxidized by oxygen with a release of energy used for charging ATP molecules. 

As a fuel, mitochondria can use glucose, fatty acids and ketone bodies (made by the liver out of fatty acids). The ketone bodies are the best fuel, but they are produced only when the level of insulin is not too high. Fatty acids are rather good too, but they are not available to the brain cells, so these cells can use only glucose and ketone bodies as fuel.

Glucose is a good fuel, but the least good of the three available kinds. When the insulin level is high, and glucose is used almost exclusively as fuel, eventually, mitochondria get damaged.

When we consume fructose, a part of it gets to mitochondria. They cannot use it as a fuel, but it harms their normal operation.

Mitochondria feel better, reproduce more actively and live longer when they burn more ketone bodies and fatty acids than glucose. Sometimes, a question is asked: Can mitochondria utilize ketone bodies alone? Some people believe that mitochondria cannot do without glucose at all. But this question does not have a practical sense. Even if we consume only fats and proteins, we still get a certain amount of glucose – from fats and some amino acids. Even when for some time (a week or two) do not eat at all and only drink water, we still obtain glucose from our storage of fats. Some amount of glucose is absolutely necessary for our red blood cells, which do not have mitochondria, and for charging ATP molecules through fermentation in case of shortage of oxygen. 

When "burnign" fuel in mitochondria, "combustion products" are produced – carbon dioxide and water, and something else, depending on the fuel. But efficiency does not reach 100%. A part of the energy of burning is released in the form of heat. But this heat is not just waste of energy, because we, homeothermic creatures (warm-blooded, that is) need heat to maintain the body temperature. It is not wasted in poikilothermic creatures (cold-blooded) either, because it helps them to speed up their biochemical processes.

Imagine a power plant, in which the generator is mechanically disconnected from the turbine (uncoupled). The fuel is burned, though, less intensively. But electricity is not produced. Only heat is. This is the idling mode.

Mitochondria can also operate in such mode. They can uncouple themselves from charging ATP molecules with energy, while continuing to burn fuel. In this case, they work at a lower load and produce only heat. Uncoupling of mitochondria is a complicated biochemical process that has nothing in common with the above comparison with an electric power plant, but its result is the same – idling mode.

But mitochondria can afford this lightened mode of operation only when there are sufficiently many of them in a cell. Then mitochondria can charge ATP molecules in turn and have some rest. Besides, if there is a need to abruptly increase charging of ATP molecules, the part of mitochondria that are resting can reconnect their "furnace" to the "generator".  

When there are few mitochondria, they have to work all the time. This leads to their faster wearing-out and further reduction of their number. And those that remain, have to work even harder. In this case, an abrupt increase of energy production is out of the question, because mitochondria already work at their full capacity. 

So, uncoupling of mitochondria (idling) is a sign of a healthy metabolism and availability of reserves. 

There are claims that, according to some research, people who live longest and preserve mental health until the last moment, have particularly many mitochondria in their cells, and a considerable part of these mitochondria at any given moment are uncoupled.

Certain substances can promote mitochondrial uncoupling. Of those that we consume with food, such are polyphenols. They are present in vegetable food, especially in greens. Plants produce them for protection of their own mitochondria and chloroplasts from damage by solar radiation (especially by ultraviolet).

It is also believed that a considerable amount of ketone bodies as fuel permits mitochondria to have rest and reproduce. And, when their number increases, they can have rest (uncouple) more frequently, increasing the available power reserve for charging ATP. 

Brown fat is a fat tissue, in the cells of which there are many mitochondria, many more than these cells need for providing energy for their lives and operation. This is because of the large number of mitochondria in these cells that this fat tissue look somewhat brown rather than white. Brown fat is always subcutaneous. 

It was established long ago that babies have a lot of brown fat. For a long time, it was believed that, with age, it disappears and becomes replaced with white fat. Now it is believed that adults may have some brown fat too. Even the elderly with healthy metabolism may have it.

In brown fat, most mitochondria are uncoupled from charging ATP. They burn the fat that is stored in the fat cells and produce heat. This is important for the babies, because they cannot increase physical activity to produce more heat when it is cold. It is less important for adults, because their muscles are sufficiently developed and they can shiver, thus increasing activity of muscles and producing more heat.  

Adults who preserved brown fat easier tolerate cold and, strangely, heat as well. When it is cold, their  subcutaneous brown fat produces more heat for warming up. When it is hot, their subcutaneous brown fat radiates more heat than absorbs.

Burning of fat by mitochondria of brown fat is not blocked by high level of insulin. Insulin blocks release of fats for other cells. But fat cells already store fat, and they do not need a special "permission" to use it as fuel. Brown fat can burn fats even when the rest of the organism cannot do this in the periods when the level of insulin is high.

Formation of brown fat is promoted by the same things that promote reproduction of mitochondria. First of all, this is normally operating system of automatic control of metabolism. If this system is broken, in the process of its repairing, some brown fat may be restored too.

Mitochondria are damaged by ionizing and ultraviolet radiation, different toxic chemicals, including those present in the tobacco smoke, so-called free radicals, as a result of long-lasting stress and/or inflammation. Also they are damaged when they work too hard charging ATP molecules by burning glucose.  Also, fructose, when it is present in blood, intervene in their operation and speeds up their damaging. And alcohol intervenes in about the same way as fructose, and with the same consequences. 

Such damages lead to reduction of the number of mitochondria and increase of the load on each of them. With time, mitochondria become unable to produce energy in the same amount as earlier. Since this energy is needed not only for motion, but also for renewal of cells and all biochemical processes in cells, the entire organism begins to work worse.

This is the disruption of metabolism. What harms metabolism, also harms mitochondria. And damaged mitochondria cannot provide normal metabolism.

Metabolism is improved when factors that damage it are removed (or, at least those that are relatively easy to remove), and also when mitochondria receive fuel that reduces their load, first of all, ketone bodies. 

Also, physical exercise and exposure to cold (cold shower), through a complicated chain of mechanisms, stimulates reproduction of mitochondria, which improve their life conditions and thus improves metabolism. 

Somewhere in 2010s, some medical scientists began to characterize the Alzheimer's disease as type three diabetes. This is because sufficiently reliable evidences emerged of a connection between steadily elevated level of blood glucose with development of this disease. It is also noted, that symptoms of this disease began to manifest in younger age. This is related to the increase of consumption of carbohydrates, especially sugar, and reduction of consumption of saturated fats two or three decades before this disease began to grow younger. This delay (two or three decades) is understandable. The brain is one of the best protected organs, and damage of metabolism causes disturbances in the brain not immediately. It could be considered a coincidence, but there are confirmation of connection of the Alzheimer's disease and abnormal metabolism at the biochemical level of nerve cells.

Other forms of dementia (and lowering of the age when their symptoms begin to manifest) are thought to be also related to metabolic disorders. Also, a connection between metabolic disorders and Parkinson's disease. Usually, several decades pass between the beginning of the metabolic disorders and first manifestations of the symptoms of these diseases. As metabolic disorders now begin earlier, so do the first symptoms of these diseases.

In many cases, a correction of metabolism that increased availability of ketone bodies to the brain cells mitigated symptoms of these diseases. 

There are certain evidences that, in people with metabolic disorders, depression and suicidal inclinations occur much more frequently than in people with healthy metabolism. There are also evidences that correction of metabolism, to an extent, helps people to overcome depression and reduces attempts of suicide.

Since the 1950s, it is known that administering the keto diet or any other diet that limits consumption of carbohydrates and replaces them with fats for people with epilepsy reduces the frequency of seizures of this disease. 

All these evidences cannot be considered scientific proofs. There are only tens of thousands of known anecdotal evidences of those who tried to repair their metabolism and felt mitigation of the mentioned symptoms and diseases, and, perhaps, several million of people who achieved similar results, but did not share their experience to avoid accusation of incompetence or even fraud.

So, no one recommends you anything. Since this is not proven, ignore this. Or do not ignore. It is up to you to decide.

Mitochondria are special structures in the cells of all living organisms, except the simplest ones – bacteria and archaea. They produce energy for charging ATP molecules.

Appearance of mitochondria became a revolution in the development of life on Earth. In fact, there was a time when mitochondria were separate bacteria, which, for some reason, settled inside larger bacteria or archaea and took upon themselves the duty to provide the larger bacteria with charged ATP molecules, while the larger bacteria provided the smaller ones with fuel. Mitochondria have a genetic code separate from that of the rest of the cell, and this code is transferred only from the mother to a child. Mitochondria inside cells live their own lives – they can merge and can reproduce (by division), they also die after a while and are replaced with young mitochondria. Their number within a cell may increase or decrease.

To charge ATP molecules with energy, mitochondria "burn" (oxidize) fuel – glucose, fatty acids and ketone bodies, for which they need oxygen. The main "combustion products" are carbon dioxide and water. This work eventually wears mitochondria out.  Not all kinds of fuel are the same to mitochondria. The best for them is ketone bodies, and the worst is glucose. It is not possible to completely eliminate glucose as a fuel for mitochondria, but an increase of the fraction of ketone bodies and decrease of the fraction of glucose improves work of mitochondria.

When there are many mitochondria, a part of them can temporarily disconnect from charging ATP molecules (uncouple). At that, they continue burning fuel for their own needs and in smaller quantity. While doing this, they produce heat. But when it is necessary to speed up charging of ATP molecules, mitochondria can quickly switch from idling to work. When there are few mitochondria, they work all the time. In this case, they do not have a reserve for charging ATP, and also they wear up faster.

Metabolism and mitochondria are tightly related. What harms mitochondria, also harms metabolism. Metabolic disorders caused by excess consumption of carbohydrates, especially sugar and fructose, damages mitochondria, which leads to worsening of metabolic disorders. 

There are many evidences of the connection between metabolic disorders and mental and psychological disorders. There are also evidences that repair of metabolism noticeably alleviates manifestation of mental and psychological disorders, if not cures them.