FIGURE 2.

Crosstalk between NADPH oxidase and mitochondria-derived ROS. NADPH oxidase activation, by endogenous and exogenous stimulation (for example Ang II), produces ROS, which stimulate PKC, MAPK, and JNK, leading to the increase in Mito-ROS production (see the text). ROS, released from mitochondria, activate redox-sensitive PKC and c-SRC, which phosphorylate NADPH oxidases and increase ROS production by NADPH oxidases. The Mito-ROS trigger NADPH oxidases activation and generation of ROS and vice versa, resulting in a vicious circle (thick gray lines). The converged increase in ROS contributes to the pathogenesis of MetS, CVD, and CKD, among others. In addition to PKC, other potential molecules (listed in the gray box) relay the signaling between NADPH oxidase and mitochondria. ROS generated by either NADPH oxidase or mitochondria exert their individual actions, such as signaling, adaptive responses, and pathophysiological responses (very thin gray line arrows). 4-HNE, 4-hydroxynonenal; 8-OHdG, 8-hydroxy-20-deoxyguanosine; Adaptive Resp, adaptive responses; CKD, chronic kidney disease; c-SRC, proto-oncogene tyrosine-protein kinase; CVD, cardiovascular disease; MAPK, mitogen-activated protein kinase; PM, plasma membrane and other cellular membranes (Mem), such as in endoplasmic reticula, endosomes etc; MetS, metabolic syndrome; Mito-ROS, ROS generated from mitochondria (right side); NADPH Oxidase-ROS, ROS generated from NADPH oxidases (left side); NP, nanoparticles or microparticles; Patho Resp, pathological responses; PKC, protein kinase C. For simplicity, other ROS-generating sources and enzymatic and non-enzymatic antioxidants are not shown.