Mitochondrial ROS Generation and Its Regulation: Mechanisms Involved in H₂O₂Signaling

Abstract

Mitochondria are the main source of reactive oxygen species in the cell. These reactive oxygen species have long been known as being involved in oxidative stress. This is a review of the mechanisms involved in reactive oxygen species generation by the respiratory chain and some of the dehydrogenases and the control by thermodynamic and kinetic constraints. Mitochondrial ROS produced at the level of the bc1 complex as well at the level of complex I are discussed. It was recognized more than a decade ago that they can also function as signaling molecules. This signaling role will be developed both in terms of mechanism and in terms of mitochondrial ROS signaling. The notion that hydrogen peroxide acts not only as a damaging oxidant but also as a signaling molecule was proposed more than a decade ago. Hydrogen peroxide signaling can be either direct (oxidation of its target) or indirect (involving peroxiredoxins, for example). The consequences of ROS signaling on crucial biologic processes such as cell proliferation and differentiation are discussed.

Loss of Drosophila i-AAA protease, dYME1L, causes abnormal mitochondria and apoptotic degeneration

“…3 To test whether the impaired complex I leads to elevated ROS level in dYME1L del flies, we used a colorimetric aconitase assay to indicate the status of oxidative damages in dYME1L del flies (Figure 5c). Mitochondrial aconitase activity was indistinguishable between young wildtype flies and dYME1L del flies.…”

“…Another challenge is the production of reactive oxygen species (ROS), the unavoidable by-products of electron transfer, which are generated mainly at complex I (NADH/ ubiquinone oxidoreductase) and complex III (ubiquinol-cytochrome c oxidoreductase) in the ETC. 3 Excessive ROS can damage proteins and impair mitochondrial functions.…”

Intracellular redox equilibrium is essential for the constitutive expression of AP-1 dependent genes in resting cells: Studies on TGF-β1 regulation

“…The ability of increased ROS to modulate different aspects of cell function has been widely recognized (11,26,37,38,40). Our group has contributed to the knowledge of this regulation by demonstrating that H 2 O 2 induces mesangial cell contraction (6), stimulates cell proliferation (8) To decreased intracellular ROS concentration, CAT was added to the extracellular media of the cells.…”

“…ROS are derived from several compartments inside the cells: mitochondria, peroxisomes, plasma membrane, endoplasmic reticulum, Golgi complex, lysosomes and the nucleus, where there are enzyme systems that synthesize ROS (7,26,37). Although this synthesis is usually considered as a whole, probably the different enzymes are responsible for ROS production for specific cellular functions.…”

“…Some of these species, such as superoxide and hydroxyl radicals, are extremely unstable, whereas others like hydrogen peroxide (H 2 O 2 ) are relatively long-lived and freely diffusible (7). They are generated in cells as a consequence of their basal function, as they are synthesized by a wide variety of enzymatic systems such as NAD(P)H oxidase, xanthine oxidase and arachidonic acid metabolizing enzymes as well as by the mitochondrial respiratory chain (7,26,38,41). Degradation of these ROS is also regulated by antioxidant enzymes, including superoxide dismutase, catalase (CAT) and glutathione peroxidase, among others.…”