Regulation of NADPH oxidases in skeletal muscle

• Skeletal muscle cells express Nox1, Nox2, and Nox4 isoforms and subunits.
• Nox2 and Nox4 are critical sources of skeletal muscle ROS in health and disease.
• Recent studies suggest unique aspects of Nox2 and Nox4 in skeletal muscle.
• Several studies suggest a cross-talk between Nox2 and mitochondrial ROS.

The only known function of NAD(P)H oxidases is to produce reactive oxygen species (ROS). Skeletal muscles express three isoforms of NAD(P)H oxidases (Nox1, Nox2, and Nox4) that have been identified as critical modulators of redox homeostasis. Nox2 acts as the main source of skeletal muscle ROS during contractions, participates in insulin signaling and glucose transport, and mediates the myocyte response to osmotic stress. Nox2 and Nox4 contribute to skeletal muscle abnormalities elicited by angiotensin II, muscular dystrophy, heart failure, and high fat diet. Our review addresses the expression and regulation of NAD(P)H oxidases with emphasis on aspects that are relevant to skeletal muscle. We also summarize: i) the most widely used NAD(P)H oxidases activity assays and inhibitors, and ii) studies that have defined Nox enzymes as protagonists of skeletal muscle redox homeostasis in a variety of health and disease conditions.