RESUMO
A bioenergetic mechanism for development of urgent and long-term adaptation to hypoxia is considered. Hypoxia induces reprogramming of respiratory chain function and switching from oxidation of NAD-related substrates (complex I) to succinate oxidation (complex II). Transient, reversible, compensatory activation of respiratory chain complex II is a major mechanism of urgent adaptation to hypoxia necessary for 1) succinate-related energy synthesis in conditions of oxygen deficiency and formation of urgent resistance in the body; 2) succinate-related stabilization of HIF-1alpha and initiation of its transcriptional activity related with formation of long-term adaptation; 3) succinate-related activation of a succinate-specific receptor CPR91. Therefore succinate is a signaling molecule, which effects are realized at three levels in hypoxia, intramitochondrial, intracellular and intercellular. Tactics and strategy for the antihypoxic defense and development of antihypoxants with energotropic action are considered.
