**9. Conclusions**

In conclusion, here we emphasize the necessity of maintaining a proper function of cardiac mitochondria even in situations with limited oxygen supply, such as heart ischemic disease. Since it is known that mitochondria have a crucial role in the adaptation process of the heart in unfavorable conditions, the idea of a positive effect of partial oxygen deprivation was studied in new therapeutic approaches. The expression of hypoxic genes and the preference of anaerobic glycolysis associated with the regulation of mPTP are considered as the key mechanisms. The previous findings sugges<sup>t</sup> that not only functional, but also structural changes in cardiac mitochondria are involved in the adaptation process. This knowledge is supported by the relation of mitochondrial membrane composition and functional properties of the heart. The composition of the cardiolipin structure, the amount of mtCx43, and the degree of mitochondrial membrane fluidity affect the formation and opening of mPTP, which is reflected in ATP synthase activity and mitochondrial survival.

**Author Contributions:** Conceptualization, M.F. and M.J.; resources, M.F., M.J., N.A., and B.S.B.; writing, review and editing, M.F., M.J., N.A., and B.S.B.; visualization, M.F.; supervision, M.F.; project administration, M.F.; funding acquisition, M.F.

**Funding:** This research was supported by the Scientific Grant Agency of the Ministry of Education, Science Research and Sport of the Slovak Republic VEGA 2/0121/18, VEGA 2/0158/19 and the Slovak Research and Development Agency APVV 15-0119; as well as projects of Structural Funds ITMS 26230120009.

**Conflicts of Interest:** The authors declare no conflict of interest.
