Mitochondria-targeted antioxidant peptides

Abstract

Overproduction of reactive oxygen species (ROS) under pathophysiologic conditions is part of the disease process. These ROS are released from different sources, and in particular from mitochondria. Although the molecular mechanisms responsible for mitochondria-mediated disease processes are unclear, oxidative stress seems to play an important role. ROS are essential to cell function, but adequate levels of antioxidant defenses are required in order to avoid the harmful effects that excessive ROS production can produce. Mitochondrial oxidative stress damage and dysfunction contribute to a number of cell pathologies that manifest themselves through a range of conditions. The antioxidants available until now have not proved to be particularly effective against many of these disorders. It is possible that these antioxidants do not reach the sites of free radical generation, especially when mitochondria are the primary source of ROS. Recent developments in mitochondria-targeted antioxidants have moved closer to providing protection against mitochondrial oxidative damage. The SS (Szeto-Schiller) peptide antioxidants represent a novel approach that employs the targeted delivery of antioxidants to the inner mitochondrial membrane. These SS peptides scavenge hydrogen peroxide and peroxynitrite and inhibit lipid peroxidation. By reducing mitochondrial ROS, they inhibit mitochondrial permeability transition and cytochrome c release, thus preventing oxidant-induced cell death. Preclinical studies support the use of these peptides for ischemia-reperfusion injury and neurodegenerative disorders. Although peptides have often been considered to be poor drug candidates, the few that have been studied are promising agents for the treatment of diseases.