Mitochondria have various shapes, generally linear, granular or short. The diameter of mitochondria is generally 0.5 ~ 1.0 μ m, and the length varies greatly, generally, it is 1.5 ~ 3 μ m, and the length can reach 10μm, while the mitochondria of human fibroblasts are longer, reaching 40 μ m. Different tissues sometimes have abnormally enlarged mitochondria under different conditions, which are called giant mitochondria.
In most cells, mitochondria are evenly distributed in the whole cytoplasm, but in some cells, mitochondria are unevenly distributed, and sometimes mitochondria gather at the edge of cytoplasm. In cytoplasm, mitochondria tend to be concentrated in areas with active metabolism, because these areas need more ATP. For example, there are many mitochondria in muscle fibers of muscle cells. In addition, sperm cells, flagella, cilia and the base of renal tubular cells have many mitochondria. Mitochondria are not only distributed in areas where ATP is needed, but also concentrated in areas where there are many oxidation substrates, such as fat droplets, because there are a lot of fat in fat droplets to be oxidized.
Generally speaking, cells must have energy supply to be active. Mitochondria are organs that generate energy in cells, and the scientific community has also named mitochondria "power room", which is the power factory of cells. The number of mitochondria in a cell ranges from a dozen to hundreds. The more active a cell is, the more mitochondria it contains. For example, beating heart cells and brain cells that often think about problems contain the most mitochondria, while skin cells contain fewer mitochondria. Scientists have found that the mitochondria of farmers' skin cells are damaged much more than those of other indoor professionals because they work outdoors all the year round. When mitochondria are damaged, cells will die due to lack of energy. Our face is exposed all the year round, and it is always attacked by wind, rain and various pollution particles, so facial cells often die prematurely because of excessive pain.
Morphology and distribution
Mitochondria are generally granular or rod-shaped, but according to biological species and physiological state, they can also be circular, dumbbell-shaped, linear, branched or other shapes. The main chemical components are protein and lipids, in which protein accounts for 65-70% of the dry weight of mitochondria and lipids account for 25-30%. Generally, the diameter is 0.5~ 1μm, and the length is 1.5~3.0μm, which can be as long as 10~20μm in pancreatic exocrine cells, so it is called giant mitochondria. The number is usually hundreds to thousands, and the number of mitochondria in plants is relatively small because of chloroplasts; There are about 1300 mitochondria in hepatocytes, accounting for 20% of the cell volume. There are only 1 single cell flagellates, and yeast cells have a large mitochondrial branch, with a huge deformation of 500 thousand; Many mammals have no mitochondria in their mature red blood cells. Usually combined with blood vessels, distributed in areas with strong cell function. For example, it is evenly distributed in liver cells, parallel or grid-like in kidney cells, bipolar in intestinal epidermal cells, concentrated at the top and bottom, and distributed in the middle of flagella in sperm. Mitochondria can migrate to functional areas in cytoplasm, and microtubules are its guide rails, powered by motor proteins.
ultra microstructure
Mitochondria are surrounded by inner and outer membranes, including outer membrane, inner membrane, membrane gap and matrix. The content of protein in mitochondria of hepatocytes is as follows: matrix 67%, intima 2 1%, adventitia 8% and membrane gap 4%.
1, the outer membrane contains 40% lipid and 60% protein, and there is a hydrophilic channel composed of porin, which allows molecules with molecular weight below 5KD to pass through, and molecules with molecular weight below 1KD can pass through freely. The marker enzyme is monoamine oxidase. It is a unit membrane structure surrounded by mitochondria. It is 6nm thick, flat and smooth, with macroporous protein on it, which can let molecules with relative molecular weight of about 5kDa pass through. There are also some enzymes that synthesize lipids and enzymes that convert lipids into enzymes that can be further metabolized in the matrix.
2. The intima contains more than 100 polypeptides, and the ratio of protein to lipid is higher than 3: 1. The cardiolipin content is high (up to 20%) and it lacks cholesterol, which is similar to bacteria. The permeability is very low, and only uncharged small molecules are allowed to pass through. Macromolecules and ions need a special transport system when they pass through the intima. For example, pyruvate and pyrophosphate are transported by H+ gradient. The electron transport chain of mitochondrial oxidative phosphorylation is located in the inner membrane, so the inner membrane plays a major role in energy conversion. The marker enzyme of intima is cytochrome c oxidase. It is a unit membrane structure located in the inner layer of the outer membrane, with a thickness of about 6nm. The permeability of intima to substances is very low, and only uncharged small molecular substances can pass through. The intima folds inward to form many ridges, which greatly increases the surface area of the intima. The intima contains three functional proteins: ① enzymes that carry out oxidation reactions in the respiratory chain; ②ATP synthase complex; ③ Some special transporters regulate the output and input of metabolites in the matrix.
3. Membrane space is a cavity between intima and adventitia, extending to the axis of crista, and the width of the cavity is about 6-8nm. Because the outer membrane has a large number of hydrophilic pores communicating with the cytoplasm, the pH value of the membrane gap is similar to that of the cytoplasm. The label enzyme is adenylate kinase. It is the inner space of mitochondria surrounded by intima and crista, and contains a lot of protein and lipids. Enzymes that catalyze the oxidation of fatty acids and pyruvate in the tricarboxylic acid cycle also exist in the matrix. In addition, it also contains mitochondrial DNA, mitochondrial ribosome, tRNAs, rRNAs and various enzymes expressed by mitochondrial genes. The labeled enzyme in the matrix is malate dehydrogenase.
4. Matrix is a space surrounded by intima and crista. Except glycolysis in cytoplasm, other biological oxidation processes are carried out in mitochondria. Enzymes that catalyze the tricarboxylic acid cycle and the oxidation of fatty acids and pyruvate are all located in the matrix, and their marker enzyme is malate dehydrogenase. Matrix has a complete transcription and translation system. Including mitochondrial DNA(mtDNA), 70S ribosome, tRNAs, rRNA, DNA polymerase, amino acid activating enzyme and so on. The matrix also contains fibers and dense particles with high electron density, and contains Ca2+, Mg2+ and Zn2+ plasmas. The structure formed by the folding of mitochondrial intima to matrix is called crista, and the formation of crista greatly increases the surface area of intima. Ridges can be arranged in two ways: one is sheet and the other is tubular. In higher animal cells, they are mainly arranged in sheets, most of which are perpendicular to the long axis of mitochondria. Tubular arrangement is common in protozoa and plants. In different kinds of cells, the number, shape and arrangement of mitochondrial cristae vary greatly. Generally speaking, cells that need more energy not only have more mitochondria, but also have more mitochondrial ridges. There are many regularly arranged granules on the crista intima of mitochondria, which are called mitochondrial granules, and the distance between each granule is about 10 nm. The basic particle, also called coupling factor 1 (F 1 for short), is actually ATP synthase, also called F0F1ATPase complex, which is a multi-component complex.
Mitochondrial semi-autonomy
1963 after the discovery of mitochondrial DNA by M. and S. Nass, people found a complete set of equipment for DNA replication, transcription and protein translation in mitochondria, such as DNA(mtDNA polymerase, RNA polymerase, tRNA, ribosome and amino acid activating enzyme), which indicated that mitochondria had an independent genetic system.
Although mitochondria can also synthesize protein, their synthetic ability is limited. Mitochondrial 1000 protein, only a dozen of them are self-synthesized. Mitochondrial ribosomal proteins, aminoacyl-trna synthetases and many structural proteins are encoded by nuclear genes, synthesized in cytoplasm and transported to mitochondria directionally, so mitochondria are called semi-autonomous organelles.
Cultured cells with labeled amino acids, chloramphenicol and cycloheximide inhibited the synthesis of protein in mitochondria and cytoplasm, respectively. It is found that human mitochondrial DNA encodes three subunits of cytochrome c oxidase, two subunits of F0, seven subunits of NADH dehydrogenase and cytochrome b 13 polypeptides. In addition, mitochondrial DNA can also synthesize 12S and 16SrRNA and 22 kinds of tRNA.
The MtDNA molecule is a circular double-stranded DNA molecule, with the outer ring being a heavy chain (H) and the inner ring being a light chain (L). The gene arrangement is very compact, and there is no intron sequence except a small area related to mtDNA replication and transcription. Each mitochondria contains several m tDNA, and the m tDNA of animals is about 16-20kb. Most genes are transcribed by H chain, including two rrna, 14 tRNA and 12 mRNA encoding polypeptides, while the L chain encodes another eight tRNAs and one polypeptide chain. The genes on mtDNA are interconnected or separated by only a few nucleotide sequences, some polypeptide genes overlap each other, and almost all reading frames lack untranslated regions. Many genes do not have a complete termination code, but only end with T or TA, and the termination signal of mRNA is added in the post-transcriptional processing.
Mitochondria are very similar to bacteria in morphology, dyeing reaction, chemical composition, physical properties, active state and genetic system, so people speculate that mitochondria originated from endogenesis. According to this view, aerobic bacteria may have been swallowed by primitive eukaryotic cells and evolved into mitochondria in a long-term and mutually beneficial life. Aerobic bacteria gradually lost their independence in the process of evolution, and transmitted a lot of genetic information to host cells, forming the semi-autonomy of mitochondria.
Mitochondrial genetic system does have many characteristics similar to bacteria, such as: ①DNA is a circular molecule with no intron; ② The ribosome is 70S type; ③RNA polymerase was inhibited by ethidium bromide, but not by actinomycin D; ④tRNA and aminoacyl tRNA synthetases are different from those in cytoplasm; ⑤ The initial aminoacyl tRNA synthesized in protein is N- formylthioyl tRNA, which is sensitive to chloramphenicol, a bacterial protein synthesis inhibitor, but insensitive to cycloheximide, a cytoplasmic protein synthesis inhibitor.
In addition, the genetic code of mammalian mtDNA is different from the universal genetic code as follows: ①UGA is not a termination signal, but a tryptophan code; ② Methionine in polypeptide is encoded by two codons, AUG and AUA, and the initial methionine is encoded by four codons, namely AUG, AUA, AUU and AUC. ③AGA and AGG are not codons of arginine, but stop codons. There are four stop codons (UAA, UAG, AGA, AGG) in mitochondrial cryptosystem.
MtDNA is maternal inheritance. Its mutation rate is higher than that of nuclear DNA, and it lacks repair ability. Some hereditary diseases, such as Leber's hereditary optic neuropathy and myoclonic epilepsy, are all related to mitochondrial gene mutation.
Mitochondrial proliferation
Mitochondrial proliferation is the division of existing mitochondria, which has the following forms:
1, partition wall separation. During mitosis, the intima first folds toward the center, and mitochondria are divided into two types, which are common in mouse liver and plant tissues.
2. Separated after contraction, found in the mitochondria of ferns and yeast.
3, budding, seen in yeast and moss, mitochondria appear small buds, and grow into mitochondria after falling off.
Mitochondria are linear, long rod-shaped, oval or round, surrounded by double-layer boundary membrane. The outer membrane is smooth, and the inner membrane is folded into ridges with different lengths, and the basal granules are attached. Between the intima and adventitia is the outer chamber of mitochondria, which is connected with the inner cavity of crista, and the inner chamber (stroma chamber) is the inner limiting membrane. In endocrine cells that synthesize steroid hormones (such as adrenal cortical cells, oval follicular cells, leydig cells, etc. ), the mitochondrial crest is tubular. The permeability of intima and adventitia is different. The outer membrane has high permeability, which allows many substances to pass through, while the inner membrane constitutes an obvious permeability barrier, which makes some substances such as sucrose and NADH completely unable to pass through, while other substances such as Na+ and Ca 2+ can only pass through active transport. The matrix of mitochondria contains electron-dense unstructured particles (matrix particles), which have high affinity with divalent cations such as Ca2+ and Mg2+. β oxidation, oxidative decarboxylation, citric acid cycle and urea cycle are carried out in the matrix. The outer membrane of mitochondria contains monoamine oxidase and various transferases of sugar and lipid metabolism. On the internal limiting membrane, there are respiratory chain and oxidative phosphorylase.
Mitochondria is one of the most sensitive organelles to various injuries. The most common pathological changes in the process of cell injury can be summarized as changes in the number, size and structure of mitochondria:
1. The average life span of mitochondria is about 10 days. Decaying mitochondria can be supplemented by directly dividing the retained mitochondria into two parts. Under pathological conditions, the proliferation of mitochondria is actually an adaptive response to chronic nonspecific cell injury, or a manifestation of enhanced cell function. For example, myocardial mitochondrial hyperplasia in valvular heart disease and mitochondrial hyperplasia in skeletal muscle with intermittent claudication in peripheral blood circulation disorder.
In the case of disintegration or autolysis of mitochondria during acute cell injury lasting about 65438 05 minutes, the number of mitochondria decreased. Due to the gradual proliferation of mitochondria during chronic injury, mitochondria generally do not decrease (even increase). In addition, the decrease of mitochondria is also a manifestation of cell immaturity and/or dedifferentiation.
2. Changes in size The most common change in cell damage is mitochondrial enlargement. According to the site of mitochondrial involvement, it can be divided into two types: matrix swelling and crista swelling, the former is more common. When the matrix swells, the mitochondria become bigger and rounder, the matrix becomes shallower, and the cristae become shorter and less or even disappear (Figure 1-9). In the case of extreme swelling, mitochondria can be transformed into small vacuolar structures. This type of swelling is part of the change of cell edema. The tiny particles in the so-called turbid swollen cells seen under the optical microscope are swollen mitochondria. Crest swelling is rare. At this time, the swelling is confined to the internal space of the crista, which makes the flat crista become flask-shaped or even vacuolar, while the matrix is more dense. Crest swelling is generally reversible, but when the membrane injury is aggravated, it can be transformed into matrix type by mixed type.
Mitochondria are extremely sensitive to injury, and their swelling can be caused by many injury factors, the most common of which is hypoxia. In addition, microbial toxins, various poisons, radiation and osmotic pressure changes can also be caused. However, mild swelling may sometimes be a manifestation of enhanced function, while obvious swelling is always a manifestation of cell damage. However, as long as the injury is not too serious and the injury factor does not act for too long, the swelling can still be recovered.
The increase of mitochondria is sometimes adaptive hypertrophy caused by the increase of organ function load, and at this time the number of mitochondria tends to increase, for example, when organ hypertrophy occurs. On the other hand, when organs atrophy, mitochondria atrophy decreases.
3. The structural change of mitochondrial crista is an obvious index of energy metabolism, but the increase of crista is not always accompanied by the increase of respiratory chain enzymes. The parallel increase of crista intima and enzyme reflects the aggravation of cell function load, which is the expression of adaptive state; On the other hand, if the increase of crista intima and enzyme is not parallel, it is a manifestation of cytoplasmic adaptive dysfunction, and cell function has not increased at this time.
In acute cell injury (mostly poisoning or hypoxia), the crista of mitochondria is destroyed; When chronic sublethal cell injury or nutritional deficiency occurs, the protein synthesis of mitochondria is hindered, so that mitochondria can hardly form new cristae.
According to the type and nature of cell injury, pathological inclusions can be formed in mitochondrial matrix or crista. Some of these inclusions are crystalline or submicroscopic (probably composed of protein), which are found in mitochondrial myopathy or progressive muscular dystrophy, and some are amorphous electronic dense substances, which are the products of the disintegration of mitochondrial components (lipids and protein) when cells tend to necrosis, and are regarded as the manifestations of irreversible damage to mitochondria. Another common change of mitochondrial injury is the formation of myelin-like layered structure, which is the result of mitochondrial membrane injury.
Rotten or damaged mitochondria are finally autophaged by cells and finally degraded and digested by lysosomal enzymes.
How mitochondria make energy
We breathe all the time, with the purpose of inhaling oxygen into the body to make ATP, an energy molecule that can be used by organisms. Oxygen is used by mitochondria to produce energy, just like burning coal to generate electricity in a power plant. There are two main components involved in energy production in mitochondria, one is called respiratory chain and the other is called ATPase. As the name implies, the respiratory chain is a component that directly uses oxygen to burn food. The food contains solar energy solidified by photosynthesis. Burning food is like the role of coal-fired boilers in power plants. The purpose is to release the solidified solar energy and promote the generator to generate electricity. Atpase is essentially a molecular motor that can generate electricity. Just like a coal-fired boiler drives a generator to rotate to generate current, solidified solar energy is released to drive a molecular motor to rotate to generate energy molecule ATP. Each of us consumes about the same amount of energy molecule ATP as our body weight every day. Therefore, mitochondria need to continuously produce ATP molecules to maintain vitality.
Mitochondria and aging
Mitochondria are parts that directly use oxygen to make energy, and more than 90% of the oxygen inhaled into the body is consumed by mitochondria. However, oxygen is a "double-edged sword". On the one hand, organisms use oxygen molecules to generate energy, on the other hand, oxygen molecules will produce extremely active intermediates (reactive oxygen radicals) in the process of being used, which will cause harm to organisms and cause oxygen poisoning. In order to survive and develop, organisms constantly struggle with oxygen toxicity, and the existence of oxygen toxicity is the original reason for the aging of organisms. Mitochondria are constantly damaged by oxygen toxicity when using oxygen molecules. When the damage of mitochondria exceeds a certain limit, cells will age and die. Organisms always have new cells to replace aging cells to maintain the continuation of life, which is the metabolism of cells.
Mitochondria and Beauty
Keeping mitochondria intact means keeping cells alive, and having healthy skin cells means keeping youth. Only by savoring it carefully can we benefit from this truth. The metabolism of skin cells is a natural process of skin renewal. When the metabolism is vigorous, the cells are updated quickly, and there are always some new cells on the face, which looks beautiful and young.