capítulos de libros
Mitochondrial nitric oxide and redox signalling modulation of cell behavior
Nitric Oxide, Cell Signaling, and Gene Expression
Año: 2006; p. 45 - 75
Mitochondria are the central organelles in cell bioenergetics. Most of available oxygen is consumed in the electron transfer chain and is placed in the inner membrane of the two membranes that limit the differentiated mitochondrial compartment. Electron transfer through mitochondrial complexes I¡VIV is joined to proton pumping across the inner membrane creating a proton electrochemical gradient between the intermembrane space and the matrix. This gradient (~0.15 V) is dissipated by the reentry of protons through ATPase channels that couple ATP synthesis to the electron transfer activity. From a classic perspective, it is accepted that the rate of this process is regulated by O2 and substrate availability as well as ADP/ATP ratio in response to cell demands. In the last few years, significant modulatory effects of nitric oxide (NO) resulted from its high-affinity binding to cytochrome oxidase, the final electron acceptor of electron transfer chain (1). In addition, mitochondria produce oxygen active species by auto-oxidation of ubisemiquinone, a transitional intermediary redox state of membrane ubiquinol. About 2 to 3% of utilized O2 undergoes one-electron reduction by ubisemiquinone, forming superoxide anion (O2 ƒ{) (Reactions 3.1 and 3.2). Most of O2 ƒ{ƒnis dismutated by mitochondrial superoxide dismutase (Mn-SOD) to H2O2, which is freely diffusible to cytosol (2); in addition, mitochondrial O2 ƒ{ƒncan be driven to cytosol through voltage-dependent anion channels (3). The ubisemiquinone pool and O2 - production rate are increased by utilization of specific compounds, such as antimycin, which blocks electron flow between cytochromes b and c (2). In addition to reversible inhibition of cytochrome oxidase, NO reportedly induced inhibitory effects onthe b-c1 region at complex III, leading to direct ubiquinol oxidation (4, 5). Considering that NO metabolism involves regulatory aspects on O2 uptake and O2 /H2O2 production in mitochondria, and the effects of H2O2 on gene expression and cell signaling, it is surmised that mitochondrial NO has a significant role in the modulation of life processes.