Succinate:
quinone reductase (SQR) of Complex II occupies a unique central point in the mitochondrial respiratory system as a major source of electrons driving
reactive oxygen species (ROS) production. It is an ideal pharmaceutical target for modulating ROS levels in normal cells to prevent oxidative stress-induced damage or alternatively,increase ROS in
cancer cells, inducing cell death.The value of drugs like
diazoxide to prevent ROS production,protecting normal cells, whereas
vitamin E analogues promote ROS in
cancer cells to kill them is highlighted. As pharmaceuticals these agents may prevent degenerative disease and their modes of action are presently being fully explored. The evidence that SDH/Complex II is tightly coupled to the
NADH/NAD+ ratio in all cells,impacted by the available supplies of Krebs cycle intermediates as essential
NAD-linked substrates, and the
NAD+-dependent regulation of SDH/Complex II are reviewed, as are links to the
NAD+-dependent
dehydrogenases, Complex I and the E3 dihiydrolipoamide
dehydrogenase to produce ROS. This review collates and discusses diverse sources of information relating to ROS production in different biological systems, focussing on evidence for SQR as the main source of ROS production in mitochondria, particularly its relevance to protection from oxidative stress and to the mitochondrial-targeted anti
cancer drugs (mitocans) as novel
cancer therapies [corrected].