Fig. 2.

Updated working scheme for sites of ROS/reactive nitrogen species (RNS) generation by skeletal muscle demonstrating the potential role of Nox2 and Nox4 isoforms of NADPH oxidase in generating superoxide in mitochondria and cytosol and acknowledging the lack of evidence for any release of superoxide from mitochondrial during contractile activity. NO, nitric oxide; ONOO⁻, peroxynitrite; ecSOD, extracellular SOD; eNOS, endothelial NO synthase; nNOS, neuronal NO synthase; PLA₂, phospholipase A₂; GPx, glutathione peroxidase; CAT, catalase; IMS, intermembrane space. [Modified from Jackson (33).]