Mitochondria and cytosol metabolic processes require the import/export of metabolites across the impermeable inner mitochondrial membrane. The transport of these molecules is performed by a family of membrane transporters known as the mitochondrial carriers (MCs), which act as master regulators of cell metabolism in health and disease. Further, MCs are key players in the reprogramming of cell metabolism that occurs in cancer. Several of them are overexpressed in various cancer types as essential gatekeepers of the trafficking of metabolic intermediates. These represent promising targets to develop novel therapies aimed at restoring the physiological metabolic processes, reducing cancer cell proliferation and metastasis formation.
In this framework, in the last few years we employed a computation approach to uncover the structural determinants of endogenous and exogenous (drug-like) ligands recognition of several members of this protein family. In addition, we also developed a computational protocol for the de-orphanization of transporters whose ligand is still unknown with the aim of uncovering novel mitochondrial metabolic pathways. Prominent results of these activities will be illustrated and discussed.
11/06/2025