Uncovering the function of the mitochondrial protein VDAC in health and disease: From structure-function to novel therapeutic strategies

Many cancer cells undergo re-programing of metabolism and develop cell survival strategies involving anti-apoptotic defense mechanisms, a hallmark of a great majority of cancer types. Regulation of mitochondrial physiology requires an efficient exchange of molecules between mitochondria and the cytoplasm across the outer mitochondrial membrane (OMM). The voltage-dependent anion channel 1 (VDAC1), an OMM protein, serves as a mitochondrial gatekeeper, controlling the metabolic and energy cross-talk between mitochondria and the rest of the cell thus playing a crucial role in the regulation of metabolic and energetic functions of mitochondria. VDAC is also recognized to function in mitochondria-mediated apoptosis and in apoptosis regulation via interaction with anti-apoptotic proteins. Thus, VDAC appears to be a convergence point for a variety of cell survival and cell death signals, mediated by its association with various ligands and proteins. Indeed, standing at the crossroad between mitochondrial metabolite transport and apoptosis VDAC1 is emerging as an excellent target for impairing the re-programed metabolism of cancer cells and their ability to evade apoptosis. As such, VDAC is an emerging as a rational target for novel therapeutics.

The aim of this Research Topic is to thoroughly review of current knowledge on VDAC1 functions in health and cancer, while unraveling common features towards precision cancer therapeutic strategies. These strategies include impair energy and metabolic homeostasis, leading to arrest cancer cell growth and tumor development, as well as interfering with anti-apoptotic proteins defense mechanism thereby overcoming the resistance of cancer cell to chemotherapy.