I will list some of the main primary consequences of hypoxia for cells and the body as a whole.
1. Activation of an energy-dependent, regulated process of programmed cell death – apoptosis, which is safe for the surrounding tissues and for the organism as a whole, as a result of external influences. Apoptosis is not self-destruction of a cell, but it killing by external factors, in the extreme case, apoptosis can be considered as forcing cells to commit suicide by external factors: – the main physiological – cortisol (circadian rhythm), which with age increasingly becomes pathological (age-dependent growth basal level of cortisol and distress), and the main pathological one – hypoxia.
There is not enough oxygen for the simultaneous work of all cells of the body, it is necessary to save the “most valuable” ones, getting rid of ineffective cells for the survival of the body under hypoxic conditions, and also get rid of cells that may be restored from stem cells. Cascade mechanisms of the sequential elimination of cell components in a certain order require the expenditure of free energy in the form of ATP hydrolysis (for example, ubiquitin).
1.1. Activation of the production of free oxygen radicals by the respiratory chain of dying mitochondria. Free radicals of oxygen (* OH) and nitrogen (* NO), possessing high values of the oxidative potential, as well as ATP and NAD(P)H are mass carriers of free energy and are involved in the normal energy metabolism of cells. Free oxygen radicals generated by dying mitochondria are products of cell apoptosis, but not vice versa, as is often found in the literature.
It is the oxygen deficiency that leads to a network of events ending in apoptosis: – slowing down of the transport of electrons along the respiratory chain; – a decrease in the electrochemical potential difference of hydrogen ions on the inner mitochondrial membrane; – swelling of mitochondria with disruption of the integrity of the outer mitochondrial membrane; – exit from the intermembrane space into the cytoplasm of cytochrome C, which leads to disconnection from the respiratory chain of cytochrome oxidase and to the termination of direct transfer of electrons to oxygen (disconnection of cytochrome oxidase from the respiratory chain is an elegant evolutionary device that excludes the possibility of senseless and therefore harmful “eating” oxygen that is already deficient under conditions of hypoxia); – activation of the reverse transfer of electrons (against the redox potential of the electron carriers of the respiratory chain) entering the respiratory chain from dehydrogenases of the second conjugation point; – increasing the concentration of the reaction product of one-electron reduction of Coenzyme Q; – chemical reaction of oxygen with the Coenzyme Q radical, leading to an increase in the concentration of free oxygen radicals.