Abstract
Reactive oxygen species (ROS) that exceed the antioxidative capacity of the cell can be harmful and are termed oxidative stress. Increasing evidence suggests that ROS are not exclusively detrimental, but can fulfill important signaling functions. Recently, we have been able to demonstrate that a NADPH oxidase-like enzyme (termed Yno1p) exists in the single-celled organism Saccharomyces cerevisiae. This enzyme resides in the peripheral and perinuclear endoplasmic reticulum and functions in close proximity to the plasma membrane. Its product, hydrogen peroxide, which is also produced by the action of the superoxide dismutase, Sod1p, influences signaling of key regulatory proteins Ras2p and Yck1p/2p. In the present work, we demonstrate that Yno1p-derived H2O2 regulates outputs controlled by three MAP kinase pathways that can share components: the filamentous growth (filamentous growth MAPK (fMAPK)), pheromone response, and osmotic stress response (hyperosmolarity glycerol response, HOG) pathways. A key structural component and regulator in this process is the actin cytoskeleton. The nucleation and stabilization of actin are regulated by Yno1p. Cells lacking YNO1 showed reduced invasive growth, which could be reversed by stimulation of actin nucleation. Additionally, under osmotic stress, the vacuoles of a ∆yno1 strain show an enhanced fragmentation. During pheromone response induced by the addition of alpha-factor, Yno1p is responsible for a burst of ROS. Collectively, these results broaden the roles of ROS to encompass microbial differentiation responses and stress responses controlled by MAPK pathways.
Highlights
NADPH oxidases are a class of enzymes that consist of six to seven transmembrane helices that coordinate two non-identical heme b molecules via four highly conserved histidines
In a previous study [5], we have shown that the Reactive oxygen species (ROS) produced by the NADPH oxidase
Our experiments suggest that the localized activity of Yno1p is required for stabilization of cortical bulk of actin, which would be expected to promote the increase in cell polarization that occurs during filamentous growth
Summary
NADPH oxidases are a class of enzymes that consist of six to seven transmembrane helices that coordinate two non-identical heme b molecules via four highly conserved histidines. The first NADPH oxidase was identified in humans because a lack of this enzyme’s activity is the main driver of chronic granulomatous disease that leads to death during early childhood, which has been attributed to a multitude of infections. Leukocytes of these patients have a defect in the enzyme Nox and, lack the ability to perform a respiratory burst that is an important parameter of the innate immune defense [2,3,4]. Confirming our result, homologous NADPH oxidases have been identified in other mono-cellular ascomycetes [6] and even bacteria [7]
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