VDACs, or Voltage-Dependent Anion Channels are the most abundant pore-forming proteins of the Mitochondrial Outer Membrane (MOM). High conserved through evolution, in mammals three distinct genes encode for three different VDAC isoforms, namely VDAC1, VDAC2, and VDAC3. VDAC1 serves as the main gate in the MOM for metabolites, such as ATP/ADP and NAD+/NADH, but also Krebs cycle's intermediates, cholesterol and glutamate. Furthermore, by interaction with many cytosolic enzymes, such as Hexokinases (HK), Glucokinase (GK), and Creatine Kinase (CK), VDAC1 provides the ATP source essential for enzyme's activity. In addition, VDAC1 represents a hub protein that interacts with over 15 other proteins including phosphorylated tau, Aβ, and γ-secretase, and participates in their toxicity. Therefore, regulation of VDAC1 is crucial not only for metabolic functions of mitochondria, but also for cell survival.