Cross talk between mitochondria and NADPH oxidases

Abstract

Reactive oxygen species (ROS) play an important role in physiological and pathological processes. In recent years, a feed-forward regulation of the ROS sources has been reported. The interaction between main cellular sources of ROS, such as mitochondria and NADPH oxidases, however, remain obscure. This work summarizes the latest findings on the role of crosstalk between mitochondria and NADPH oxidases in pathophysiological processes. Mitochondria have the highest levels of antioxidants in the cell and play an important role in the maintenance of cellular redox status, thereby acting as an ROS and redox sink and limiting NADPH oxidase activity. Mitochondria, however, are not only a target for ROS produced by NADPH oxidase but also a significant source of ROS, which under certain condition may stimulate NADPH oxidases. This crosstalk between mitochondria and NADPH oxidases, therefore, may represent a feed-forward vicious cycle of ROS production which can be pharmacologically targeted under conditions of oxidative stress. It has been demonstrated that mitochondria-targeted antioxidants break this vicious cycle, inhibiting ROS production by mitochondria and reducing NADPH oxidase activity. This may provide a novel strategy for treatment of many pathological conditions including aging, atherosclerosis, diabetes, hypertension and degenerative neurological disorders in which mitochondrial oxidative stress seems to play a role. It is conceivable that the use of mitochondria-targeted treatments would be effective in these conditions.

Uric acid induces fat accumulation via generation of endoplasmic reticulum stress and SREBP-1c activation in hepatocytes

“…Mitochondrial oxidative stress, which is generally known to occur later than ROS production by membranous NOX activation, and which can be also induced by membranous NOX-mediated ROS in part, is reported as a key mechanism of hepatic steatosis. 30,31 In our study, TUDCA ameliorated mitochondrial ROS production (Figure 9), suggesting ER stress preceded mitochondrial dysfunction. Antioxidants, NAC, DPI, and rotenone alleviated uric acidinduced TG accumulation in HepG2 cells.…”

SK3 channel and mitochondrial ROS mediate NADPH oxidase-independent NETosis induced by calcium influx

“…There have been numerous reports describing the cross-talk between mitochondrial superoxide and NOX activity (34)(35)(36). In endothelial cells, mitochondrial superoxide can stimulate cytoplasmic NOX (36).…”

Reactive Oxygen Species in Inflammation and Tissue Injury

“…MtROS has also been implicated in increasing oxidative stress through cross-talk with nitric oxide synthases (NOSs) (293 the macrophage inflammatory response that contributes to insulin resistance and atherogenesis (293). Recent reports have highlighted an interesting concept of cross-talk between MtROS and NADPH oxidase, which can drive both feed-forward and feedback regulations of NADPH oxidases (73,96). Ang II-stimulated mitochondrial H 2 O 2 was blocked by NADPH oxidase inhibitor apocynin and protein kinase C inhibitor chelerythrine (96).…”

“…Recent reports have highlighted an interesting concept of cross-talk between MtROS and NADPH oxidase, which can drive both feed-forward and feedback regulations of NADPH oxidases (73,96). Ang II-stimulated mitochondrial H 2 O 2 was blocked by NADPH oxidase inhibitor apocynin and protein kinase C inhibitor chelerythrine (96). Moreover, depletion of p22 phox with siRNA also inhibited Ang II-mediated MtROS production (100).…”

“…Moreover, depletion of p22 phox with siRNA also inhibited Ang II-mediated MtROS production (100). In contrast, ROS produced by the mitochondria on serum withdrawal has been shown to trigger NOX1 activation (96). Moreover, Ang II-mediated mitochondrial dysfunction has been shown to increase the expression and activity of NOX1 and NOX4 in vascular smooth muscle cells (96).…”