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Mitochondrial Proteins

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Mitochondrial Proteins

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Mitochondrial Proteins Background

Mitochondrion is a two-layer membrane organelle that exists in most cells. It is the structure that makes energy in cells. It is the main place for cells to perform aerobic respiration. It is called "power house". Its diameter is around 0.5 to 1.0 microns. Except for E. histolytica, Giardia lamblia and several microsporidia, most eukaryotic cells have mitochondria more or less, but their respective mitochondria are in size, quantity and appearance. It's all different. Mitochondria have its own genetic material and genetic system, but its genome size is limited and it is a semi-autonomous organelle. In addition to energizing cells, mitochondria are involved in processes such as cell differentiation, cell signaling, and apoptosis, and have the ability to regulate cell growth and cell cycle.

Mitochondrial proteinFigure 1. Number 9 in the figure is mitochondria.

Distribution

The direction of mitochondria distribution is consistent with that of microtubules, usually distributed in areas with strong cell functions: in the kidney cells, close to the microvessels, arranged in parallel or grid; in the epithelial cells of the intestinal epithelium, it is distributed in the poles and concentrated in the apex and base; Distributed in the middle of the flagella. In the in vitro culture of oocytes, as the cells mature, the mitochondria will develop into a uniform distribution from the periphery of the cells. Mitochondria can move from microtubules in the cytoplasm and are powered by motor proteins to migrate to functional areas.

Structure

Mitochondria can be divided into four functional regions: mitochondrial outer membrane (OMM), mitochondrial membrane gap, mitochondrial inner membrane (IMM) and mitochondrial matrix from the outside to the inside. The membranes on the outside of the mitochondria are parallel to each other and are typical unit membranes. Among them, the mitochondrial outer membrane is smoother and acts as an organelle membrane; the mitochondrial inner membrane forms mitochondrial ridges inwardly, which bears more biochemical reactions. The two membranes divide the mitochondria into two compartments. Between the two mitochondrial membranes is the mitochondrial membrane gap, which is surrounded by the mitochondrial inner membrane.

Mitochondrial proteinFigure 2. Structure of mitochondrion.

Functions

1. Energy conversion

Mitochondria are the sites of oxidative metabolism of eukaryotes, and are the sites where sugars, fats, and amino acids ultimately oxidize to release energy. The common pathway responsible for the ultimate oxidation of mitochondria is the tricarboxylic acid cycle and oxidative phosphorylation, corresponding to the second and third phases of aerobic respiration, respectively. Complete glycolysis in the cytoplasmic matrix and the completed tricarboxylic acid cycle in the mitochondrial matrix produce reduced nicotinarnide adenine dinucleotide (NADH) and reduced flavin adenine dinucleoside High-energy molecules such as reduced flavin adenosine dinucleotide (FADH2), and the step of oxidative phosphorylation is the use of these substances to reduce oxygen release energy to synthesize ATP. During aerobic respiration, one molecule of glucose releases 30-32 molecules of ATP after glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation (considering that it may take 2 molecules of ATP to transport NADH into mitochondria). If the cell is in an oxygen-deficient environment, it will turn to anaerobic respiration. At this time, the pyruvic acid produced by glycolysis no longer enters the carboxylic acid cycle in the mitochondria, but continues to react in the cytoplasmic matrix (reduced by NADH into a fermentation product such as ethanol or lactic acid), but does not produce ATP. Therefore, in the process of anaerobic respiration, 1 molecule of glucose can only produce 2 molecules of ATP in the first stage.

2. Tricarboxylic acid cycle

Each molecule of pyruvic acid produced in glycolysis is actively transported across the mitochondrial membrane. After entering the mitochondrial matrix, pyruvate is oxidized and combined with coenzyme A to form CO2, reduced coenzyme I and acetyl-CoA. Acetyl-CoA is the primary substrate for the Krebs cycle (also known as the "citric acid cycle" or "Krebs cycle"). The enzymes involved in this cycle are freed from the mitochondrial matrix except for the succinate dehydrogenase located in the mitochondrial inner membrane. In the tricarboxylic acid cycle, each molecule of acetyl-CoA is oxidized to produce a reduced cofactor (including 3 molecules of NADH and 1 molecule of FADH2) and 1 molecule of guanosine triphosphate (GTP), which initiate the electron transport chain.

3. Storage of calcium ions

Mitochondria can store calcium ions and interact with structures such as endoplasmic reticulum and extracellular matrix to control the dynamic balance of calcium ion concentration in cells. The ability of mitochondria to rapidly absorb calcium ions makes it a buffer zone for calcium ions in cells. Driven by the mitochondrial membrane potential, calcium ions can be transported into the mitochondrial matrix by unidirectional transporters present in the mitochondrial inner membrane; when mitochondrial matrices are ejected, sodium-calcium exchange proteins are required or calcium-induced calcium release (calcium) -induced-calcium-release, CICR) mechanism. When calcium ions are released, it causes a "calcium wave" that is accompanied by a large membrane potential change, which activates certain second messenger system proteins, coordinates the release of neurotransmitters such as synapses, and hormones in endocrine cells. secretion. Mitochondria are also involved in calcium signaling during apoptosis.

Mitochondria and aging

Mitochondria are sites that use oxygen to make energy directly, and more than 90% of the oxygen inhaled in the body is consumed by the mitochondria. However, oxygen is a "double-edged sword". On the one hand, organisms use oxygen molecules to make energy. On the other hand, oxygen molecules generate extremely active intermediates (active oxygen radicals) in the process of being used, which can cause oxygen toxicity. The organism seeks to survive and develop in the struggle against oxygen toxicity. The existence of oxygen toxicity is the most original cause of organism aging. Mitochondria use oxygen molecules and are also constantly exposed to oxygen toxicity. When mitochondrial damage exceeds a certain limit, cells will die of aging. The organism always has new cells to replace the aging cells to maintain the continuation of life, which is the metabolism of the cells.

Mitochondria and disease

Mitochondrial problems in human mitochondria can lead to mitochondrial disease. Mitochondrial disease is a large class of genetic metabolic diseases. Mitochondrial diseases mainly include: maternal hereditary Leigh syndrome, mitochondrial myopathy, multisystem diseases, cardiomyopathy, progressive extraocular muscle paralysis, Leer inheritance. Sexual optic neuropathy, mitochondrial myopathy, myopathy, diabetes and deafness, ataxia chorea, extracellular matrix chronic migratory erythema, progressive extraocular muscle paralysis, myoglobinuria motor neuron disease, iron granule cells Anemia, MERRF-mitochondrial myopathy, myoclonus (epilepsy), mitochondrial myopathy, MERRF, mitochondrial myopathy, ataxia complicated with retinitis pigmentosa, familial bilateral striatum necrosis, ataxia and pigmentation Retinitis, familial bilateral striatum necrosis, skeletal muscle lysis, sudden infant death syndrome and other diseases.

References:

1. Sanchis-Gomar F.; et al. Mitochondrial biogenesis in health and disease. Molecular and therapeutic approaches. Current Pharmaceutical Design. 2014, 20 (35): 5619-33.

2. Gardner A.; et al. Is a 'Mitochondrial Psychiatry' in the Future. Curr. Psychiatry Rev. 2005, 1 (3): 255-271.

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