NapA Mediates a Redox Regulation of the Antioxidant Response, Carbon Utilization and Development in Aspergillus nidulans

Abstract

The redox-regulated transcription factors (TFs) of the bZIP AP1 family, such as yeast Yap1 and fission yeast Pap1, are activated by peroxiredoxin proteins (Prxs) to regulate the antioxidant response. Previously, Aspergillus nidulans mutants lacking the Yap1 ortholog NapA have been characterized as sensitive to H2O2 and menadione. Here we study NapA roles in relation to TFs SrrA and AtfA, also involved in oxidant detoxification, showing that these TFs play different roles in oxidative stress resistance, catalase gene regulation and development, during A. nidulans life cycle. We also uncover novel NapA roles in repression of sexual development, normal conidiation, conidial mRNA accumulation, and carbon utilization. The phenotypic characterization of ΔgpxA, ΔtpxA, and ΔtpxB single, double and triple peroxiredoxin mutants in wild type or ΔnapA backgrounds shows that none of these Prxs is required for NapA function in H2O2 and menadione resistance. However, these Prxs participate in a minor NapA-independent H2O2 resistance pathway and NapA and TpxA appear to regulate conidiation along the same route. Using transcriptomic analysis we show that during conidial development NapA-dependent gene expression pattern is different from canonical oxidative stress patterns. In the course of conidiation, NapA is required for regulation of at least 214 genes, including ethanol utilization genes alcR, alcA and aldA, and large sets of genes encoding proteins involved in transcriptional regulation, drug detoxification, carbohydrate utilization and secondary metabolism, comprising multiple oxidoreductases, membrane transporters and hydrolases. In agreement with this, ΔnapA mutants fail to grow or grow very poorly in ethanol, arabinose or fructose as sole carbon sources. Moreover, we show that NapA nuclear localization is induced not only by oxidative stress but also by growth in ethanol and by carbon starvation. Together with our previous work, these results show that SakA-AtfA, SrrA and NapA oxidative stress-sensing pathways regulate essential aspects of spore physiology (i.e., cell cycle arrest, dormancy, drug production and detoxification, and carbohydrate utilization).

Tolerance to alkaline ambient pH in Aspergillus nidulans depends on the activity of ENA proteins

“…Our previous work demonstrated that enaA expression is independent of CrzA 16 . AtfA of A. nidulans was characterized as a candidate transcription factor acting downstream of HogA/SakA MAPK and playing a role in oxidative and osmotic stress responses 19,38,44 . Expression of enaA has been shown to be independent of AtfA, but enaB and enaC displayed AtfA-dependent expression especially in response to oxidative stress 38 .…”

DnmA and FisA Mediate Mitochondria and Peroxisome Fission, and Regulate Mitochondrial Function, ROS Production and Development in Aspergillus nidulans

“…Our work has been oriented to demonstrate that ROS play critical signaling roles in cell differentiation (Hansberg and Aguirre, 1990;Aguirre et al, 2005;Mendoza-Martinez et al, 2017;Mendoza-Martínez et al, 2019). In one approach, we have used the filamentous fungi Aspergillus nidulans to study the mechanisms by which cells perceive and respond to external ROS.…”

Redox Proteomic Analysis Reveals Oxidative Modifications of Proteins by Increased Levels of Intracellular Reactive Oxygen Species during Hypoxia Adaptation of Aspergillus fumigatus

“…However, an ortholog of Tir1 does not exist in the genome of A. fumigatus . In general, Yap1 seems to act not only as an important regulator of the antioxidative stress response, but also as a regulator of several other pathways including carbon utilization and asexual sporulation as shown in Aspergillus nidulans …”