Redox Regulation of Mitochondrial Function

Abstract

Redox-dependent processes influence most cellular functions, such as differentiation, proliferation, and apoptosis. Mitochondria are at the center of these processes, as mitochondria both generate reactive oxygen species (ROS) that drive redox-sensitive events and respond to ROS-mediated changes in the cellular redox state. In this review, we examine the regulation of cellular ROS, their modes of production and removal, and the redoxsensitive targets that are modified by their flux. In particular, we focus on the actions of redox-sensitive targets that alter mitochondrial function and the role of these redox modifications on metabolism, mitochondrial biogenesis, receptor-mediated signaling, and apoptotic pathways. We also consider the role of mitochondria in modulating these pathways, and discuss how redox-dependent events may contribute to pathobiology by altering mitochondrial function. Antioxid. Redox Signal. 16, 1323-1367.

Reactive Oxygen Species in Inflammation and Tissue Injury

“…O 2 2 is generated by one-electron reduction of O 2 through enzymatic catalysis by NADPH oxidase or xanthine oxidase (XO) or during electron transfer reactions in the ETC of mitochondria ( Fig. 1) (163,233,413 and O 2 . However, this reaction is thermodynamically unfavorable under the physiological conditions (209).…”

“…There are four electron transport carriers that are spatially organized in order of their increasing redox potential, complex I (NADH-ubiquinone oxidoreductase), complex II (succinateubiquinone oxidoreductase), complex III (ubiquinolcytochrome c reductase), and complex IV (cytochrome c oxidase) (Fig. 3) (163). Transfer of electrons to molecular O 2 is a tightly controlled process, and only 1%-2% of electrons that leaked out in this process react with O 2 , resulting in O 2 2 (163).…”

Molecular mechanisms regulating NLRP3 inflammasome activation

“…The mitochondria are the main intracellular organelles that contribute the most to cellular ROS. 67 Previous studies showed that ROS, especially those from mitochondria, contributed to activation of the NLRP3 inflammasome. 10,12,[68][69][70] Indeed, numerous NLRP3 inflammasome activators are known to trigger mitochondrial ROS production in a variety of cells.…”

Diverting Glycolysis to Combat Oxidative Stress

“…Perturbations in mitochondrial metabolism such as changes in oxygen tension and the actions of mitochondrial uncoupling proteins can modulate superoxide production [ 5 , 6 ]. In addition, enzymes including the NADPH oxidases, which are particularly important in phagocytic cells, xanthine oxidases, uncoupled nitric oxide synthases, and cytochrome P-450s actively produce ROS [ 7 ]. Redox-active metal ions, such as iron, can generate the highly reactive hydroxyl radical from hydrogen peroxide via the Fenton reaction [ 8 ].…”