Mitochondria-targeted antioxidants as therapies

Mitochondria are central to oxidative phosphorylation and much of metabolism, and are also involved in many aspects of cell death. Consequently, mitochondrial dysfunction contributes to a wide range of human pathologies. In many of these, excessive oxidative damage is a major factor because the mitochondrial respiratory chain is a significant source of the damaging reactive oxygen species superoxide and hydrogen peroxide. However, despite the clinical importance of mitochondrial oxidative damage, antioxidants have been of limited therapeutic success. This may be because the antioxidants are not selectively taken up by mitochondria, but instead are dispersed throughout the body. To address this unmet need, a series of mitochondria-targeted antioxidants have been developed over the past few years that are selectively concentrated within mitochondria in vivo. The accumulation of an antioxidant at the site where it is needed most has been shown to improve the outcome in a large number of animal models of diseases that involve mitochondrial oxidative damage. Mitochondria-targeted antioxidants have also been developed as pharmaceuticals and have been shown to be safe and effective in human clinical trial phase IIa studies. Therefore the mitochondria-targeted antioxidants are a new class of pharmaceuticals that can be used in a wide range of human pathologies for which current therapies are of limited efficacy. Here we survey the work that has been done to date using mitochondria-targeted antioxidants and suggest future applications.