Peroxiredoxin PrxA and thioredoxin TrxA mediate the redox signal to the transcription factor NapA in the fungus Aspergillus nidulans

Ap-1-like transcription factors play a crucial role in regulating antioxidant gene expression and protecting cells from oxidative stress. Extensive research on redox regulation in Saccharomyces cerevisiae and Schizosaccharomyces pombe has revealed notable differences in their mechanisms. However, it remains unclear whether filamentous fungi share similarities with either yeast system or employ a distinct signaling strategy. To address this, we investigated the redox signal relay in Aspergillus nidulans , focusing on how peroxiredoxin PrxA and thioredoxin TrxA modulate the activity of the Ap-1-like transcription factor NapA. We demonstrate that PrxA is essential for NapA activation, transmitting the H₂O₂ signal through a disulfide bond between its peroxidatic and resolving cysteines to NapA's Cys558, which subsequently forms an intramolecular disulfide bond with Cys404. Furthermore, we reveal that TrxA, rather than Txl1, is responsible for reducing and inactivating NapA by direct interaction in both the cytoplasm and nucleus, utilizing its own catalytic cysteine residues. These findings establish a mechanistic framework for NapA activation and reduction, providing new insights into oxidative stress responses in filamentous fungi and their divergence from yeast systems.