In the process of human evolution, many microorganisms in the living environment have been absorbed into the human life system and become parasites of the human body. Mitochondria, or telomeres, are parasitic cells in most organ cells of human body.
Mitochondria, mitochondria or telomeres are semi-autonomous organelles contained in eukaryotic cells and have a double-layer membrane structure. Its inner membrane extends into the cavity to form many ridges, and its main function is to gradually release the energy stored in food decomposition products through respiration to meet the needs of various activities of body cells, so it is called "power room ro power device".
Mitochondria were first named by German scholar C Benda in 1897. Chondrion comes from the Greek mito chord.
The above picture shows a mitochondrial cell in pancreatic cells, which has an outer membrane and a mitochondrial crest with deep basal folds, expanding into a mitochondrial matrix, and the chemical reaction of mitochondrial cells producing energy occurs on the mitochondrial crest.
Mitochondria is the most complex biological machine in human cells, and it is also the most surprising. We used to know that mitochondria are related to human life span. Generally speaking, the longer the mitochondria, the longer the life span, and there is a positive correlation.
Now more research by Howard Hughes Institute of Harvard Medical School has found that when mitochondria function normally, it will provide enough energy for human cells to consume; When mitochondrial function is abnormal, it will bring a series of neurodegenerative diseases, diabetes, cancer, change the immune response, and even accelerate aging. (Related to neurodegenerative diseases, diabetes, cancer, changes in immune response and even aging)
Mitochondria generate metabolic energy by oxidizing carbohydrates, protein and fatty acids. In the five-step chemical reaction of respiratory chain, mitochondrial organelles capture oxygen, and together with glucose and fatty acids, they generate a complex organic chemical substance-adenosine triphosphate (ATP), which is used as fuel to supply human life.
Now recognize the five-step respiratory chain chemical reaction to release energy. It consists of electron transporters and hydrogen transporters, most of which are protein with auxiliary groups. These auxiliary groups undergo redox due to the addition or removal of electrons or hydrogen atoms (electrons+protons). NADH or FAD provided by tricarboxylic acid cycle or fatty acid oxidation enters the respiratory chain and finally combines with oxygen through the transfer of electrons and H+. When electrons pass through the respiratory chain, energy is gradually released. Most of the released energy is converted into ATP in time, which is called oxidative phosphorylation.
The main components of respiratory chain are: ① pyridine-nucleotide linked dehydrogenase, ② flavoprotein, ③ ferritin, ④ coenzyme Q and ⑤ cytochrome (including cytochrome A, B and C). At present, there are different views and questions about the arrangement order of respiratory chain components, which may not be completely correct.
Without the help of mitochondrial organelles, cells in the body can quickly and conveniently produce energy based on glycogen through an anaerobic process called glycolysis, but the efficiency is too low. Mitochondrial organelles catalyze the same glycogen by oxidation, which can generate 15 times the energy for human cells.
This advantage of energy conversion is considered to have been formed 654.38+0 billion years ago or 654.38+0.5 billion years ago. When a single free-living bacterium enters a single cell organ with its nucleus and forms a * * * life with * * * glory, it exists. Bacteria entering the nucleus of single-celled organs (now mitochondria) become organelles in the nucleus.
This relationship exists not only in all animal cells, but also in all plant cells and fungal cells. (Plants and Fungi)
This * * * relationship also brings disadvantages. Just as opening a window brings fresh air, flies, mosquitoes and bad smells may come in. Some human diseases, such as Lyme disease, arthritis, typhus and chlamydia infection, are related to this. These diseases are called mitochondrial diseases. For example, tetracyclines and antibiotics are harmless to healthy people, but people with mitochondrial diseases need to be careful to avoid them.
① The first case of mitochondrial disease
In May, 1958, a 30-year-old Swedish woman came to Rolf Luft Clinic in Karolins, near Stockholm, and told the doctor that she always felt a persistent fever. According to the record, the patient told the doctor that she began to have this symptom when she was 7 years old. She saw many doctors, but the reason was unknown.
Ruft measured the patient's body temperature and skin temperature, and noticed that although she had been eating, the patient was still thin and did not gain weight. Because of the loss of water and liquid caused by sweating a lot, she needs to drink a lot of water constantly. Although patients are often in a state of lethargy, the basal metabolic rate of patients is still twice that of normal people, and the heart rate exceeds 100 times per minute.
Ruft's biopsy of skeletal muscle showed that there were abnormally large and excessively aggregated mitochondrial organelles on the mitochondrial cristae of patients' cells.
Why do patients always feel hot? This may be because mitochondrial organelles with higher density and size than normal level produce more cellular energy and release it into the body.
In the end, Ruft was at the end of his rope. He doesn't know how to improve the symptoms of patients with mitochondrial diseases and reduce the heating efficiency of mitochondria. In the end, he could only provide ice cubes to cool down, and the patient then set himself on fire.
In nature, there is a plant-skunk cabbage, which carries a special kind of mitochondria, which can heat itself and raise the temperature of plants by 30 degrees Celsius. The heat of plants can melt the surrounding snow and release the mixture in plants to attract pollinators to pollinate. (pollinator)
② Mitochondrial researchers realize that the heating capacity of mitochondria is best moderate, which can not only meet the energy demand of living cells in the body, but also avoid burning too much to make the body empty.
Perhaps it is the interaction between mitochondrial genes and the environment in the process of evolution, so specific mitochondrial gene mutations are chosen to adapt to the special environment, such as smelly tobacco in winter.
In a study on the mitochondria of experimental animals in 2005, the researchers gave one group of experimental animals the ability to run for a long distance, while the other group gave mitochondrial genes such as diabetes and obesity, which began to be fixed after 1 1 generation inheritance. 1 1 generation is equivalent to 275 years of human beings, but it is only a blink of an eye in the process of evolution.
In the United States, mitochondrial diseases caused by mitochondrial gene mutations affect about 50 thousand patients. This rare disease (too rare to attract market-driven drugs to cure) is fatal to patients and confusing to doctors. Because even if two patients with mitochondrial defects have the same genetic test, one may be impaired vision and hearing, neurodegeneration, myocardial disease and dysphagia; Another possibility is that the vision is impaired, and other organ systems are still good.
Because all tissues in our body have mitochondrial cells, which generate energy for body cells, once your mitochondrial protein group and protein group are defective, some organs of the body will be affected.
These mitochondrial diseases were originally called maternal genetic diseases, because mitochondrial DNA was only inherited from the mother, and this inference can be traced back to the maternal ancestor mitochondrial Eva of human beings. (Mitochondrial Eve)
With the development of genetic science, people know more and more about organelle genes. Researchers believe that many mitochondrial diseases can also be inherited through paternal lines, because most mitochondrial protein is actually composed of DNA in the nucleus, not mitochondrial DNA.
It has been found that mitochondrial diseases are related to many diseases, including diabetes, heart disease, Parkinson's disease and Archie Harmo's disease, hearing loss and mental disorders including depression.
With the development of mitochondrial research, researchers have found that mitochondria have many functions besides generating energy.
As the coding structure of protein, mitochondrial gene is the main functional unit of mitochondria in cells. 198 1 year mitochondrial genome sequencing found 13 protein, which could not explain so many mitochondrial diseases. Researchers know that mitochondria can produce 1000 kinds of protein. How to explain this gap?
The answer is thought to exist in the process of evolutionary history. 10 billion years ago, because mitochondrial cells entered organelles for parasitism, perhaps some genes were transformed from mitochondria into host cells, that is, most DNA existed in the nucleus. This mitochondrial genome transfer, from 16000 base pairs of the original DNA block, only the essence of glass remains.
Compared with the distant ancestor form of mitochondria and its surviving close relatives, such as rickettsia bacteria causing typhus, there are 6.5438+0 million base pairs, and the genome of mitochondria is very small.
Combined with the DNA in each nucleus, these ancient genes produced two-thirds of the mitochondrial protein. The other third is the invention and creation of primitive bacteria and cells in the process of evolution, which can now make mitochondria in human cells do something that their ancestors could not do.
At present, Vamsi Mootha and his team from Harvard General Hospital and Massachusetts Institute of Technology published the mitochondrial gene map of protein in 2008 1 158, and updated it in 20 15. Protein, the mitochondrial protein in all organelles, cells, tissues and organs, is called mitochondria. Mitochondria and its host cells exchange information through calcium transfer. (Calcium signal) By tracking the calcium signal, some mitochondrial genetic diseases can be found.
① Traditional mitochondrial research focuses on energy production, but it cannot explain the pathogenesis of mitochondrial diseases. Although it can be explained by insufficient energy and energy supply, it is far-fetched
Some organs with mitochondrial diseases are not necessarily the organs with the highest energy demand. Some studies have turned to the irreplaceable role of mitochondria in regulating cell death and withering, including the role of immune system and cell signal transmission.
65.438 billion years ago, when the first mitochondrial cell entered the cell host, the oxygen content in the earth's atmosphere was quite low, and then gradually increased. It is generally believed that oxygen is necessary for life. On the other hand, oxygen is corrosive. In biology, oxygen and its by-products will cause oxidative damage to cells and lead to the aging of nuclear organs.
Mitochondria are consumers of oxygen. Researchers speculate that in the process of biological evolution, the cell host chooses mitochondrial bacteria, which may not only generate energy efficiently, but also better control the side effects of oxygen.
Normal gene expression supports this view. Genes open mitochondria and at the same time open antioxidant programs. These mitochondrial genes regulate and activate the antioxidant level by increasing the number of mitochondria. For example, if you build a car with a six-cylinder engine to a V8 engine, you need a bigger catalytic converter.
The picture above shows ovarian cells, and the yellow ones are densely distributed mitochondrial organelles, and the cells are activated to secrete hormones.
② A study in 2009 found that widely used antioxidant vitamin supplements would interfere with this natural antioxidant reaction mechanism of mitochondrial organelles. In the experiment, participants were divided into four groups: those who took antioxidant vitamins such as vitamin E after exercise; Exercise without taking antioxidant vitamins; Do not exercise and take antioxidant vitamins; Do not exercise or take antioxidant vitamins.
After a few months, the two groups who exercised were healthier than the two groups who did not exercise. Interestingly, the group who exercised and did not take antioxidant vitamins had the best physical changes. Through exercise, cells outside mitochondria will also feel these stimuli, so the body will adjust to the beneficial state of a certain body organ. Taking antioxidant vitamins will interfere with this natural adaptation mechanism of body cells.
During the evolution of 654.38+billion years, mitochondria responded to pressure for countless times, so that the mutation of mitochondrial gene did not kill cells, but adopted a rescue reaction, and a series of mitochondrial chemical reactions under pressure loss produced energy. In some cases, the overload and damage paths of some organelles and host cells can provide net benefits for cells and the whole organ.
Another interesting example is the compensation mechanism of the body. (overcompensation)
Diabetes patients taking metformin will interfere with the normal mitochondrial function of the body. After taking metformin, the first step in the five-step process of mitochondria producing energy respiratory chain is destroyed, but the weak inhibition caused by metformin can trigger the adaptive mechanism of diabetic patients.
Just as people are vaccinated with antiviral vaccines, metformin causes toxic excitatory effect in vivo, which is a protective mechanism of body compensation. Some researchers went further and tried whether the toxic excitability caused by metformin could delay aging.
④ Mitochondrial gene detection (20 14) found that low atmospheric oxygen concentration can trigger a reaction of organism organs, which has a protective effect on subacute necrotizing encephalomyelitis caused by central nervous system diseases. This disease can be caused by any mutation in 75 genes, and the baby will die of respiratory failure within 3- 16 months.
When researchers used laboratory mice to check mitochondrial diseases, the results were surprising. Normal mice live for two years, while mice with mitochondrial disease only live for 55 days. When Mootha's team reduced the oxygen concentration in the air by 1 1%, which was equivalent to a plateau of14,000 feet, the researchers found that the disease could be prevented from the beginning. Mice with mitochondrial diseases lived in the air with low oxygen content for one year.
Even those experimental mice that are dying can regain their vitality by limiting their oxygen intake. Mootha is called Lazarus effect. On the other hand, taking too much oxygen will kill a mouse in a few days like poison.
The anoxic environment is also very beneficial to human beings. Mootha is studying the health impact report of Indian military personnel stationed in 12000 and 18000 feet border plateau. Compared with those who served in the plain, those who served in the plateau for a long time had a higher proportion of acute infection. However, in the long-term comparison, the number of people suffering from diabetes, stroke, heart disease and cognitive impairment in plateau areas has decreased significantly.
Data from human research and experimental mice show that too much oxygen is harmful to animals. Therefore, sometimes it is useless and harmful to use hyperbaric oxygen chamber to supplement special oxygen to treat mitochondrial diseases in hospitals. Some patients get worse or die after being treated by the manager's hyperbaric oxygen chamber. Too much oxygen will also lead to the decrease of mitochondria, which is related to the shortening of life span.
The decrease in the number of mitochondria is related to aging, and the increase in the probability of people suffering from Parkinson's disease and diabetes is due to mitochondrial dysfunction. Old people have fewer mitochondria and are less efficient than young people.
However, exercise can promote the number and length of mitochondria at any age. When your skeletal muscle cells increase mitochondria, it will eliminate the adverse effects and improve the overall efficiency.
Generally speaking, the beneficial effects of exercise and healthy diet will play a role through mitochondria.
The future prospect of mitochondrial research is attractive, and accurate mitochondrial medicine can be developed. (Precise Mitochondrial Medicine)
There are three aspects: the first is the molecular diagnosis of blood drawing; The second one can analyze the metabolic products of blood, thus judging the severity of mitochondrial dysfunction; Thirdly, targeted therapy can be developed, not only for rare and fatal mitochondrial diseases caused by mitochondrial gene mutation, but also for some common mitochondrial diseases.
For those who have no conditions to live in plateau areas, maybe the next step will be to develop hypoxia treatment.