Mitochondria and mitochondrial proteins represent a group of promising pharmacological target candidates in the search of new molecular targets and drugs to counteract the onset of hypertension and more in general cardiovascular diseases (CVDs). Indeed, several mitochondrial pathways result impaired in CVDs, showing ATP depletion and ROS production as common traits of cardiac tissue degeneration. Thus, targeting mitochondrial dysfunction in cardiomyocytes can represent a successful strategy to prevent heart failure. In this context, the identification of new pharmacological targets among mitochondrial proteins paves the way for the design of new selective drugs. Thanks to the advances in omics approaches, to a greater availability of mitochondrial crystallized protein structures and to the development of new computational approaches for protein 3D-modelling and drug design, it is now possible to investigate in detail impaired mitochondrial pathways in CVDs. Furthermore, it is possible to design new powerful drugs able to hit the selected pharmacological targets in a highly selective way to rescue mitochondrial dysfunction and prevent cardiac tissue degeneration. The role of mitochondrial dysfunction in the onset of CVDs appears increasingly evident, as reflected by the impairment of proteins involved in lipid peroxidation, mitochondrial dynamics, respiratory chain complexes, and membrane polarization maintenance in CVD patients. Conversely, little is known about proteins responsible for the cross-talk between mitochondria and cytoplasm in cardiomyocytes. Mitochondrial transporters of the SLC25A family, in particular, are responsible for the translocation of nucleotides (e.g., ATP), amino acids (e.g., aspartate, glutamate, ornithine), organic acids (e.g. malate and 2-oxoglutarate), and other cofactors (e.g., inorganic phosphate, NAD+, FAD, carnitine, CoA derivatives) between the mitochondrial and cytosolic compartments. Thus, mitochondrial transporters play a key role in the mitochondria-cytosol cross-talk by leading metabolic pathways such as the malate/aspartate shuttle, the carnitine shuttle, the ATP export from mitochondria, and the regulation of permeability transition pore opening. Since all these pathways are crucial for maintaining healthy cardiomyocytes, mitochondrial carriers emerge as an interesting class of new possible pharmacological targets for CVD treatments.

Department of Biosciences Biotechnologies Environment University of Bari Aldo Moro Via E Orabona 4 70125 Bari Italy

Department of Biosciences Biotechnologies Environment University of Bari Aldo Moro Via E Orabona 4 70125 Bari Italy; Department of Chemistry and Biochemistry Mendel University in Brno Zěmědelská 1 61300 Brno Czech Republic

Department of Pharmacy Pharmaceutical Sciences University of Bari Aldo Moro Via E Orabona 4 70125 Bari Italy

Department of Sciences University of Basilicata Viale dell'Ateneo Lucano 10‑85100 Potenza Italy

Department of Translational Biomedicine and Neurosciences University of Bari Aldo Moro Policlinico Piazza G Cesare 11 70120 Bari Italy

Institute of Biomembranes Bioenergetics and Molecular Biotechnologies 70126 Bari Italy

Polytechnic University of Bari DICATECh Via Orabona 4 70125 Bari Italy

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