This paper focuses on a bioenergetic mechanism responding to hypoxia. This response involves hypoxia-induced reprogramming of respiratory chain function and switching from oxidation of complex I (NAD-related substrate...This paper focuses on a bioenergetic mechanism responding to hypoxia. This response involves hypoxia-induced reprogramming of respiratory chain function and switching from oxidation of complex I (NAD-related substrates) to complex II (succinate oxidation). Transient, reversible, compensatory activation of respiratory chain complex II is a major mechanism of urgent adaptation to hypoxia, which is necessary for 1) succinate-related energy synthesis in the conditions of oxygen shortage and formation of urgent resistance;2) succinate-related stabilization of HIF-1α and initiation of its transcriptional activity related with formation of long-term adaptation;3) succinate-dependent activation of the succinate-specific receptor GPR91. Thus, mitochondria perform a signaling function with succinate as a signaling molecule. Effects of succinate in hypoxia occur at three levels, intramitochondrial, intracellular and intercellular. In these settings, succinate displays antihypoxic activity. The review is focused on tactics and strategy for development of the antihypoxic defense and antihypoxants with energotropic properties.展开更多
文摘This paper focuses on a bioenergetic mechanism responding to hypoxia. This response involves hypoxia-induced reprogramming of respiratory chain function and switching from oxidation of complex I (NAD-related substrates) to complex II (succinate oxidation). Transient, reversible, compensatory activation of respiratory chain complex II is a major mechanism of urgent adaptation to hypoxia, which is necessary for 1) succinate-related energy synthesis in the conditions of oxygen shortage and formation of urgent resistance;2) succinate-related stabilization of HIF-1α and initiation of its transcriptional activity related with formation of long-term adaptation;3) succinate-dependent activation of the succinate-specific receptor GPR91. Thus, mitochondria perform a signaling function with succinate as a signaling molecule. Effects of succinate in hypoxia occur at three levels, intramitochondrial, intracellular and intercellular. In these settings, succinate displays antihypoxic activity. The review is focused on tactics and strategy for development of the antihypoxic defense and antihypoxants with energotropic properties.
