Electrical control of the cell energy metabolism at the level of mitochondrial outer membrane

Abstract Energy, generated by the mitochondrial oxidative phosphorylation system, is transferred to the cytosol across the mitochondrial outer membrane (MOM), through the voltage-dependent anion channels (VDACs). The role of the VDAC's voltage-gating process to control the transfer of ATP, creatine phosphate and other negatively charged metabolites across MOM might be crucial for the cell energy metabolism regulation. However, it depends on the probability of the outer membrane potential (OMP) generation by a currently undefined mechanism that has usually been considered doubtful, based on the assumption that VDACs always stay in the electrically open state. Nevertheless, computational analysis of various possible metabolically-dependent mechanisms of OMP generation suggests that MOM is not a “coarse sieve”, but in fact it functions as an electrical gatekeeper of cell energy metabolism, due to a probable OMP-dependent VDAC's gating. OMP generation could also be involved in the control of cell death resistance and mechanisms of various diseases.