Mitochondrial Targeting of Antioxidants

Abstract

The mitochondrial matrix is the only intracellular compartment that is negatively charged compared to the cytosol. This is why any cation penetrating the mitochondrial membrane must be accumulated inside mitochondria. This principle was used to construct mitochondria-targeted antioxidants (mtAOX) composed of an antioxidant moiety and a penetrating cation with delocalized positive charge. The mtAOX most active in various in vitro tests are MitoQ and SkQ, cationic derivatives of mitochondrial ubiquinone and chloroplast plastoquinone, respectively. Their high activities are due to the fact that the reduced (active) form of MitoQ and SkQ can be regenerated by the mitochondrial respiratory chain from their oxidized forms produced as a result of the antioxidant action of these quinones. An additional important advantage of SkQ is that the “window” between antiand prooxidant activities of this compound is very much wider than that of MitoQ. Both MitoQ and SkQ have already been tested on animals to treat various diseases that seem to be caused by reactive oxygen species (ROS) produced by mitochondria. In several cases, the use of SkQ was more successful than MitoQ. In particular, it was found that SkQ prolongs the life span of various organisms (from fungi to mammals) and retards (sometimes even reverses) a group of traits typical for aging. Clinical trials of drops of an aqueous solution of SkQ as a medicine have already given a positive result in the case of the age-related disease “dry-eye syndrome.” The SkQ1-containing drops of Visomitin are now available in Russian drugstores.