Targeting antioxidants to mitochondria: A new therapeutic direction

Mitochondria play an important role in controlling the life and death of a cell. Consequently, mitochondrial dysfunction leads to a range of human diseases such as ischemia-reperfusion injury, sepsis, and diabetes. Although the molecular mechanisms responsible for mitochondria-mediated disease processes are not fully elucidated yet, the oxidative stress appears to be critical. Accordingly, strategies are being developed for the targeted delivery of antioxidants to mitochondria. In this review, we shall briefly discuss cellular reactive oxygen species metabolism and its role in pathophysiology; the currently existing antioxidants and possible reasons why they are not effective in ameliorating oxidative stress-mediated diseases; and recent developments in mitochondrially targeted antioxidants and their future promise for disease treatment. (C) 2005 Elsevier B.V. All rights reserved.