El papel de la membrana mitocondrial externa en el control del metabolismo energético celular

Abstract

Up to 95% of the energy in the eukaryotic cells is produced in the mitochondria, which are composed of two membranes, internal and external. The main function of the inner membrane is the oxidative phosphorylation. ATP and/or phosphocreatine produced in mitochondria are transferred to the cytosol across the mitochondrial outer membrane, mainly through the porins (voltage-dependent anion channel, VDAC). As the mechanisms of generation of the electrical potential on this membrane are not known, it is generally assumed that the VDAC electric gate is always open. However, the outer membrane potential (OMP) of mitochondria may be generated by various mechanisms in a manner dependent on the cell energy metabolism. OMP generation by the VDAC-hexokinase complexes in cancer cells, or by the direct oxidation of cytosolic NADH in the mitochondria of the yeast Saccharomyces cerevisiae, may explain the Crabtree and Warburg effects as an electrical suppression of mitochondria. According to the model developed, the prevention of the formation of the VDAC-hexokinase complexes may result in anti-Warburg and anti-cancer effects. In addition, the generation of the positive OMP by the VDAC-creatine kinase complexes could protect mitochondria in cardiomyocytes and other cells against toxic levels of cytosolic calcium. The mechanisms proposed for OMP generation dependent on the cell energy metabolism suggest that the VDAC electrical properties play an important role in various physiological and pathophysiological processes.