Mitochondrial Production of Reactive Oxygen Species

Reactive oxygen species (ROS) are important cellular messengers involved in the regulation of a number of both destructive and constructive cellular signaling elements and when going beyond a permissive level cause different pathologies. Since mitochondrion is thought to be one of the major sites of ROS production, it looks highly important to reveal which mitochondrial compartments are responsible for this production. Among known loci of mitochondrial ROS generation, the most significant are considered to be mitochondrial complexes I and III (located in the inner membrane), dihydroorotate dehydrogenase and dehydrogenase of a-glycerophosphate (outer surface of the inner membrane), a-ketoglutarate dehydrogenase and puruvate dehydrogenase complexes and succinate dehydrogenase (inner surface of the inner membrane), aconitase (matrix), cytochrome b5 reductase and monoamine oxidase (outer membrane). Recently discovered ROS-induced ROS release (Zorov et al. J.Exp.Med 192(7):1001-1014) observed under conditions of the induction of the permeability transition, may also originate from mitochondrial Complex I. However, the significance of ROS production by complexes I and III is quite questionable under normal cell functioning (Zorov et al. Biochemistry (Moscow) 72(10):1115-1126). Mitochondrial ROS generation by these complexes after their essential conformational changes is discussed.