The role of mitophagy in the development of COPD
Obstructive pulmonary disease and mitochondrial death
This disease is characterized by a restriction of air flow through the respiratory tract, which causes: chronic cough, shortness of breath (with little physical exertion), increased secretion of mucus in the bronchi, a gradual decrease in the elasticity of lung tissue, impaired gas exchange, pulmonary emphysema, etc. Almost always this pathology is accompanied by inflammatory phenomena that worsen the condition of the bronchial surface and bronchioles contribute to hypoventilation of the lungs, intoxication and deviation of blood parameters from the norm. In addition, the function of the respiratory muscles is disrupted and the wall of the arteries of the respiratory system thickens, which causes pulmonary hypertension to develop, leading to profound changes in the myocardium (the so-called pulmonary heart is formed). All of the above processes provoke both respiratory and heart failure, dramatically reducing the quality of life of patients and requiring long-term complex treatment (John J. Reilly, Stepping Down Therapy in COPD // N. Engl. J. Med., 2014).
There are several factors that cause the appearance of chronic obstructive pulmonary disease. Among them, long-term smoking of tobacco products (including passive) should be put in the first place. According to the scientific literature, up to 80-90% of all cases of this pathology occur due to cigarette smoke. In addition, COPD can be caused by: inhaled air pollution, occupational hazards, viral-bacterial and fungal infections, genetic predisposition, etc.
The main stages of the development of chronic obstructive pulmonary disease have long been established, but there are quite a lot of hidden links in its pathogenesis (mechanism of formation) that do not allow us to find effective treatment methods and implement them in practical medicine. This is the reason for the extremely low effectiveness of therapy and high mortality rates. Therefore, when studying this pathology, it is important to pay special attention to the state of the cells of the epithelial wall of the respiratory tract (bronchi, bronchioles, alveoli) and their organelles, primarily mitochondria. It is known that the latter are the "energy stations" of cells, that is, the place where, under the influence of numerous enzymes, organic molecules are oxidized and energy (ATP) is formed. It is necessary for the biosynthesis of proteins, enzymes, nucleic acids, as well as for all mechanisms of cell activity (growth, reproduction, protection, absorption and release of substances, etc.). The processes of formation of new mitochondria and destruction of obsolete ones proceed continuously, which allows them to maintain their quantity and efficiency at the level necessary for the cell.
A group of scientists from the USA and Canada led by Augustine M.K. Choi conducted a complex experimental study to establish the role of mitophagy (destruction of mitochondria) in the development of chronic obstructive pulmonary disease (Mizumura et al., Mitophagy-dependent necroptosis contributes to the pathogenesis of COPD // J. Clin. Invest., 2014). To do this, the above-mentioned disease was modeled in laboratory animals, and the mechanisms of division and destruction of mitochondria in the epithelium of the respiratory tract, as well as various ways of influencing these processes, were studied at the intracellular level.
As a result of the study, it was found that the factors provoking chronic obstructive pulmonary disease (in particular, tobacco smoke) repeatedly increase the intensity of mitophagy in the epithelial cells of the bronchi and bronchioles. Because of this, energy deficiency of these cells develops and their rapid death (necroptosis), causing pathological disorders of the surface of the respiratory tract and stable progression of the disease. When substances that inhibit mitophagy are introduced into the body (for example, Mdivi-1), the destruction of epithelial cells stops, and there is also no development of emphysema of the lungs, obstructive and inflammatory phenomena in the bronchi and bronchioles.
Thus, it is proved that mitophagy in the epithelial cells of the respiratory tract causes their death, and this plays a key role in the development of chronic obstructive pulmonary disease. The development of new pharmaceuticals that reduce the intensity of mitophagy will significantly improve the condition of patients and prevent the occurrence of serious complications in this pathology.
Portal "Eternal youth" http://vechnayamolodost.ru20.10.2014