The Hypoxia Signal as a Potential Inducer of Supercomplex Formation in the Oxidative Phosphorylation System of Heart Mitochondria

Abstract

A correlation between the transition of the oxidative phosphorylation system into a supercomplex state and a change of the functional state of mitochondrial energetics upon the transition from aerobic respiration to hypoxic conditions has been established for the first time. The effect was observed by two different methods in liver and heart mitochondria. The occurrence of highly ordered structures in the membranes of heart mitochondria under hypoxic conditions has been detected by small-angle neutron scattering and electron microscopy during the transition of oxidative phosphorylation into the supercomplex state. The structural parameters of cristae inferred from the data of small-angle neutron scattering and electron microscopy have been compared. The results of measurements using the two methods coincided. Successive exposure to hypoxia and weak osmotic stress signals showed a qualitative difference between these signals. Successive exposure to two signals, with hypoxia as the first one and weak osmotic stress as the second one, was shown to cause impairment of mitochondrial integrity. The effect was observed by small-angle neutron scattering and electron microscopy. Thus, we demonstrated the existence of two qualitatively different signals (hypoxia and osmotic stress), which altered the oxidative phosphorylation system and induced its transition into the supercomplex state.