Mitochondria as a Target of Intermittent Hypoxia

Abstract

The review is focused upon summarizing the current knowledge of the mechanisms of interval hypoxic training (IHT) impact on the mitochondria (Mt) structure and functions in comparison with the effects of acute hypoxia (AH). It has been revealed that AH causes mitochondrial swelling, vacuolization of organelles, disorganization and destruction of mitochondrial membranes. When exposed to IHT, the increase in the total number of mitochondria, the reduction of the number of structurally modified organelles, the appearance of energetically active Mt with vesicular cristae, and the micromitochondria (microMt) formation are observed. One of the key mechanisms of cell damage during hypoxia and reoxygenation is excessive production of reactive oxygen species (ROS) in the mitochondria which oxidize proteins, lipids and DNA. On the other hand, low level of ROS production is protective and serves as a trigger for adaptive responses. IHT leads to reprogramming of the mitochondria metabolism, ensuring adequate production of ATP. The activation of potassium transport in the mitochondrial matrix under IHT is a protective mechanism against Ca2+ overload caused by acute hypoxia. The intensity of neuronal mitochondrial energy production in the brain stem is directly related to the regulation of neurotransmitter metabolism, including glutamate and GABA, which are involved in the mechanisms of respiratory rhythmogenesis formation. All adaptive reactions to hypoxia are regulated by HIF-factors (HIF-1, HIF-2 and HIF-3). Each of HIF-subunits plays a certain role depending on the mode of hypoxia-induced stress. These peculiarities can be important when choosing a mode of IHT to prevent and treat various diseases. New data on the organ specificity of HIF operation provide potential pharmacological regulation of HIFs as a new therapeutic approach for treatment of diseases.