© 2013 Elsevier Inc. All rights reserved. A small proportion of the oxygen used by the mitochondrial respiratory chain is partially reduced to superoxide, which is then further metabolized to hydrogen peroxide. In addition to reactive oxygen species (ROS), nitric oxide synthase (NOS) produces nitric oxide (NO) which, at low concentrations, controls mitochondrial respiration and biogenesis. At higher concentrations, NO reacts with superoxide to generate a family of reactive molecules known as the reactive nitrogen species (RNS). At low levels, ROS and NO contribute to cell signaling and mitochondrial respiration and biogenesis. ROS and RNS cause DNA, lipid, and protein damage when uncontrolled and, at higher levels, contribute to bioenergetic failure in the cardiovascular and central nervous systems.