Mitochondrial Signaling and Ultrastructure in the Myocardium During Long-Term Adaptation to Hypoxia

In the myocardium of rats of two phenotypes (low and high resistance to hypoxia), the dependence of the reaction of catalytic subunits of mitochondrial enzyme complexes I-V and the severity of ultrastructural changes in mitochondria upon exposure to repeated hypoxia (20 days-three daily hourly exposures to hypoxic mixtures of -14% O₂, 10.5% O₂ and 8% O₂, equivalent to 3000 m, 5000 m and 7000 m). The dynamics of expression of catalytic subunits of mitochondrial complexes I-V and ultrastructural changes in three subpopulations of mitochondria were analyzed. During the course of exposure to hypoxia (training sessions) each repeated hypoxic exposure under any regimen caused an activation of mitochondrial complex II and mitochondrial complexes III-V. At 14-10.5% O₂, this reaction was repeated with each hypoxic exposure during 8-12 training sessions. After 20 sessions, ATP synthesis returned to its initial level, indicating the completion of adaptation. These changes correlated with optimization of the mitochondrial ultrastructure, which was most pronounced at 14% O₂. On the contrary, at 8% O₂ under conditions of inhibition of succinate dehydrogenase (mitochondrial complex II), ATP synthesis was suppressed; and pronounced structural disorders of mitochondria developed. Thus, we have demonstrated that mitochondrial enzymes and the ultrastructure of subpopulations of myocardial mitochondria are informative indicators of the functional and metabolic state of the heart.