H2O2 Induces Major Phosphorylation Changes in Critical Regulators of Signal Transduction, Gene Expression, Metabolism and Developmental Networks in Aspergillus nidulans.

Ulises Carrasco-Navarro,Jesús Aguirre

doi:10.3390/jof7080624

Ulises Carrasco-Navarro, Jesús Aguirre

Open Access

https://doi.org/10.3390/jof7080624

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Abstract

Reactive oxygen species (ROS) regulate several aspects of cell physiology in filamentous fungi including the antioxidant response and development. However, little is known about the signaling pathways involved in these processes. Here, we report Aspergillus nidulans global phosphoproteome during mycelial growth and show that under these conditions, H2O2 induces major changes in protein phosphorylation. Among the 1964 phosphoproteins we identified, H2O2 induced the phosphorylation of 131 proteins at one or more sites as well as the dephosphorylation of a larger set of proteins. A detailed analysis of these phosphoproteins shows that H2O2 affected the phosphorylation of critical regulatory nodes of phosphoinositide, MAPK, and TOR signaling as well as the phosphorylation of multiple proteins involved in the regulation of gene expression, primary and secondary metabolism, and development. Our results provide a novel and extensive protein phosphorylation landscape in A. nidulans, indicating that H2O2 induces a shift in general metabolism from anabolic to catabolic, and the activation of multiple stress survival pathways. Our results expand the significance of H2O2 in eukaryotic cell signaling.

Highlights

Aerobic organisms generate reactive oxygen species (ROS) during normal metabolism
These conditions were based on previous results showing that this H2O2 treatment induces the phosphorylation of the stress MAPK SakA [22,25] and its translocation to the nucleus, where it physically interacts with transcription factor AtfA [33], and other proteins [22] as well as the induction of catB gene expression and catalase B activity [24,27,28,33]
As MpkA T105 corresponds to Slt2 T195, our results suggests that the H2O2-induced phosphorylation of MpkA at T105 contributes to its activation

Summary

Introduction

ROS are O2 derived molecules that are produced mainly by partial reduction or excitation. Superoxide is produced during respiration and by dedicated enzymes like NADPH oxidases [1], while cellular H2O2 is generated by spontaneous or superoxide oxidase-mediated dismutation of superoxide. H2O2, considered as the most important ROS in redox biology [2], is efficiently eliminated by peroxiredoxins, peroxidases, catalaseperoxidases, and catalases. ROS were considered as harmful molecules involved in aging and pathogenic processes [4]. We and others have shown that ROS played regulatory roles in different cellular processes such as bacterial gene regulation [5,6], plant [7] and animal [8] signal transduction, and cell differentiation [9,10]

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