Peculiarities of Immediate Response of Respiratory Chain Enzymes in Rat Cerebral Cortex to Hypoxia

Abstract

We performed a complex study of the dependence of immediate reaction of catalytic subunits in mitochondrial enzymes (NDUFV2, SDHA, Cyt b, COX1, and ATP5A) in rat cerebral cortex (the most hypoxia-sensitive tissue) on the severity and duration of hypoxia in vivo and the role of individual resistance of rats to oxygen deficiency in this process. Three types of responses to hypoxia were revealed. The immediate response of mitochondria to oxygen deficiency appeared after its drop by 30-33% relatively to normal atmosphere level. It manifested in up-regulation of NAD-dependent oxidation, i.e., activation of respiratory chain complex I. Further decrease in oxygen concentration by 50% reprogrammed the work of respiratory chain via activation of respiratory chain complex II in parallel with down-regulation of the electron transport function of the respiratory chain complex I. This response was optimal for the expression of adaptation genes and for the formation of immediate tolerance of rats to hypoxia. The greatest drop of oxygen concentration by 60-62% reversed the Krebs cycle promoting recovery of the electron transport function of respiratory chain complex I. Despite this, the energy efficiency of the respiratory chain and the potency to mobilize the rapid adaptation mechanisms degraded due to abnormalities in cytochrome segment of the respiratory chain.