Inhibitors of Succinate: Quinone Reductase/Complex II Regulate Production of Mitochondrial Reactive Oxygen Species and Protect Normal Cells from Ischemic Damage but Induce Specific Cancer Cell Death

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