Mitochondria Signaling in Adaptation to Hypoxia

A bioenergetic mechanism for development of urgent 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-1 α and initiation of its transcriptional activity related with formation of urgent and long-term adaptation; 3) succinate-related activation of a succinate-specific receptor GPR91. Therefore, succinate is a signaling molecule, and its effects are realized at three levels in hypoxia, intramitochondrial, intracellular and intercellular.