**Myocardial Adaptation in Pseudohypoxia: Signaling Regulation of mPTP via Mitochondrial Connexin Cardiolipin**

#### **Miroslav Ferko \*, Natália Andelová, Barbara Szei**ff**ová Baˇcová and Magdaléna Jašová**

Center of Experimental Medicine, Slovak Academy of Sciences, Institute for Heart Research, Dúbravská cesta 9, 841 04 Bratislava, Slovakia; nat.andelova@gmail.com (N.A.); usrdbaca@savba.sk (B.S.B.); jasovam@gmail.com (M.J.)

**\*** Correspondence: usrdmife@savba.sk; Tel.: +421-907065665

Received: 7 November 2019; Accepted: 15 November 2019; Published: 17 November 2019

**Abstract:** Therapies intended to mitigate cardiovascular complications cannot be applied in practice without detailed knowledge of molecular mechanisms. Mitochondria, as the end-effector of cardioprotection, represent one of the possible therapeutic approaches. The present review provides an overview of factors affecting the regulation processes of mitochondria at the level of mitochondrial permeability transition pores (mPTP) resulting in comprehensive myocardial protection. The regulation of mPTP seems to be an important part of the mechanisms for maintaining the energy equilibrium of the heart under pathological conditions. Mitochondrial connexin 43 is involved in the regulation process by inhibition of mPTP opening. These individual cardioprotective mechanisms can be interconnected in the process of mitochondrial oxidative phosphorylation resulting in the maintenance of adenosine triphosphate (ATP) production. In this context, the degree of mitochondrial membrane fluidity appears to be a key factor in the preservation of ATP synthase rotation required for ATP formation. Moreover, changes in the composition of the cardiolipin's structure in the mitochondrial membrane can significantly affect the energy system under unfavorable conditions. This review aims to elucidate functional and structural changes of cardiac mitochondria subjected to preconditioning, with an emphasis on signaling pathways leading to mitochondrial energy maintenance during partial oxygen deprivation.

**Keywords:** cardioprotection; mitochondria; mitochondrial permeability transition pores; mitochondrial connexin 43; cardiolipin
