Modulating Mitochondrial Fission to Lower Diabetic Oxidative Stress

Mitochondria are at the crossroads of energymetabolism, and they play a major role in theregulation of cell life and death. Mitochon-drial oxidation of fat and glucose substrates generates a transmembrane electrochemical gradient, and this is used to synthesize adenosine triphosphate (ATP), the chemical fuel for cell and tissue functions. In the pro-cess, electron transfer through the mitochondrial respiratory chain is inevitably associated with production of reactive oxygen species (ROS). Several physiological roles have been described for ROS (1), but ROS generation in excess of antioxidant defenses is harmful and may cause oxidative stress with damage to DNA, lipids, proteins, and organelles (1,2). Hyperglycemia is a strong inducer of oxidative stress through enhanced ROS generation at mitochondrial as well as nonmitochondrial levels (2–4), and pathways activated by oxidative stress have a major role in the pathogenesis of diabetes complications (2,5). In addition, oxidative stress