Mitochondria-Targeted Bioactive Molecules and Redox Probes Seminar

One of these antioxidants, MitoQ, is an ubiquinone derivative targeted to mitochondria by covalent attachment to a lipophilic triphenylphosphonium cation through an aliphatic carbon chain. Due to the large mitochondrial membrane potential, the cation was accumulated within mitochondria inside cells, where the ubiquinone moiety inserted into the lipid bilayer and was reduced by the respiratory chain. The ubiquinol derivative thus formed was an effective antioxidant that prevented lipid peroxidation and protected mitochondria from oxidative damage. In cell culture studies, the mitochondrially-localized antioxidant protected mammalian cells from hydrogen peroxide-induced apoptosis. This was compared to untargeted ubiquinone analogs which were ineffective in preventing apoptosis. Selectively manipulating mitochondrial antioxidant status with targeted antioxidants is a feasible approach to investigate the role of mitochondrial oxidative damage in cell death. In addition to MitoQ, a range of other mitochondria targeted redox probes and antioxidants have since been developed. This approach may have further applications in investigating mitochondrial dysfunction in a range of experimental models.