Nox enzymes from fungus to fly to fish and what they tell us about Nox function in mammals

Abstract

The production of reactive oxygen species (ROS) in a highly regulated fashion is a hallmark of members of the NADPH oxidase (Nox) family of enzymes. Nox enzymes are present in most eukaryotic groups such as the amebozoid, fungi, algae and plants, and animals, where they are involved in seemingly diverse biological processes. However, a comprehensive survey of Nox functions throughout biology reveals common functional themes. Noxes are often activated in response to stressful conditions such as nutrient starvation, physical damage or pathogen attack. Although the end result varies depending on the organism and tissue, Nox-produced ROS mediates the response to the adverse stimuli, such as innate immunity responses in plant and animals or cell differentiation in Dictyostelium, fungi and plants. These responses involve ROS-mediated signaling mechanisms occurring at intracellular or cell-to-cell levels, and sometimes involve cell wall or extracellular matrix cross-linking. Indeed, Noxes are involved in local and systemic signaling from plants to fish, and in cross-linking of the plant hair-cell wall, synthesis of the nematode cuticle and formation the sea urchin fertilization envelope. The extensive use of Nox enzymes in biology to regulate cell-to-cell signaling and morphogenesis suggest that additional functions in mammalian signaling and development remain to be discovered.

An injury-response mechanism conserved across kingdoms determines entry of the fungus Trichoderma atroviride into development

“…Various studies have shown that antioxidants inhibit conidiation in Neurospora crassa, and the lack of antioxidant enzymes results in higher levels of ROS and enhanced cell differentiation, whereas elimination of prooxidant enzymes results in arrested cell differentiation (8,9).…”

“…NADPH oxidases (Noxs) are the most important enzymes capable of producing ROS (9). The damaging effects of ROS on cell components and their role in aging are well established.…”

“…The damaging effects of ROS on cell components and their role in aging are well established. However, there is increasing evidence supporting an alternative view, in which the production of ROS by Noxs regulates cell differentiation, among other functions (9).…”

“…The Nox enzyme family was originally related to responses to exposure to pathogens in both plants and animals, resulting in the generation of high levels of ROS (2,9). In animals, Noxs are activated upon mechanical injury, producing high levels of ROS, which may aid in sterilization of the wound and serve as a chemotactic signal to recruit neutrophils (9).…”

“…In animals, Noxs are activated upon mechanical injury, producing high levels of ROS, which may aid in sterilization of the wound and serve as a chemotactic signal to recruit neutrophils (9). In plants, Noxs have a variety of functions, including response to wounding, herbivory and programed cell death (PCD), where ROS produced by Noxs forms a gradient of H 2 O 2 , indicating that it functions as propagation signal (2,9). Fungi contain from one to three Nox genes (noxA, noxB, noxC), depending on the species (8), and a NoxR protein that regulates NoxA/NoxB (10).…”