Fig. 1

ROS production in mitochondria. Mitochondria is the primary source for ROS production. There are nine different types of enzymes that have the capacity to generate ROS. Among them, some are present on outer mitochondrial membrane (OMM) i.e. Cytochrome b5 reductase and monoamine oxidases (MAO) and while other found in inner membrane, i.e. dihydroorotate dehydrogenase (DHOH), dehydrogenase of α-glycerophosphate (α-GDH), succinate dehydrogenase (SDH), aconitase, α-ketoglutarate dehydrogenase complex (KGDHC), Complex-I and Complex-III. MAO, DHOH and α-GDH produces H₂O₂ via direct or indirect biochemical reactions, while cytochrome b5, Complex-I and complex-III produce superoxides. Complex-I produced superoxides in presence of NADH and require tightly bounded ubiquinone. Rotenone can block electron transport by inhibiting ubiquinone and produce ROS, and requires a high degree of redox reduction on the rotenone binding site. The second process involved in ROS production from Complex-I has been known as ‘reverse electron transfer (RET)’. In RET, electrons are transferred against the flow of redox potentials of electron carriers (i.e. from reduced co-enzyme Q to NAD⁺ not to oxygen). Complex-III can produce a lot of superoxides during Q-cycle (a multifarious reaction system involved oxidation of coenzyme Q while, cytochrome c acts as electron carrier/acceptor) that rapidly generate H₂O₂ by dismutation. Antimycin can inhibit the quinone reducing site and lead to accumulation of unstable semiquinone and stimulate superoxide production. In the same way KCN and oligomycin can inhibit electron transfer in complex-IV and V respectively, leading to ROS production. SDH is thought to produce ROS via its FAD, while aconitase generate hydroxyl radical by releasing Fe²⁺. PDHC and KGDHC can produce both superoxides as well as hydrogen peroxide. After generation, superoxide can react with many available molecules or free radicals to form different types of free radicals who can accelerate the cellular damage. To cop superoxide, manganese superoxide dismutase (MnSOD) can convert superoxide to hydrogen peroxide that can be additional converted to water and oxygen by the action of several enzymes like catalase (CAT) or glutathione peroxidase (GPX). For further details, see the text