NOXases

NOXases, or NADPH oxidases, are a family of membrane-bound enzymes that catalyze the transfer of electrons from NADPH (nicotinamide adenine dinucleotide phosphate) to molecular oxygen, producing reactive oxygen species (ROS) such as superoxide anion (O₂⁻). These enzymes play a critical role in cellular redox signaling and host defense mechanisms, particularly in immune cells like neutrophils and macrophages.

The primary function of NOXases is to generate ROS, which serve as signaling molecules in various physiological processes, including cell proliferation, differentiation, and apoptosis. They also contribute to pathogen elimination by oxidizing microbial components during phagocytosis. NOXases are composed of multiple subunits, with the catalytic subunit, NOX (or gp91phox in humans), being essential for electron transfer. Additional regulatory subunits, such as p47phox, p67phox, p40phox, and the small GTPase Rac, assemble at the plasma membrane to activate the enzyme upon appropriate stimuli.

There are seven known NOX isoforms in mammals: NOX1, NOX2 (formerly known as gp91phox), NOX3, NOX4, NOX5, DUOX1, and DUOX2. Each isoform exhibits distinct tissue distribution and regulatory mechanisms. For example, NOX2 is predominantly expressed in phagocytic cells, while NOX4 is widely distributed and involved in non-phagocytic ROS production. Dysregulation of NOXase activity has been implicated in various pathological conditions, including chronic inflammatory diseases, cardiovascular disorders, and cancer.

NOXases are regulated at multiple levels, including transcriptional, post-translational, and assembly-dependent mechanisms. Oxidative stress, cytokine signaling, and mechanical stimuli can modulate their activity, contributing to both protective and detrimental effects in disease progression. Research into NOXase function continues to uncover their complex roles in health and disease, offering potential therapeutic targets for conditions linked to oxidative imbalance.