A heme oxygenase-like protein is involved in oxidative stress protection and Cryptochrome-related ROS signaling in Aspergillus nidulans

In this work, HoxB, a heme oxygenase-like protein, was investigated. Heme oxygenase typically catalyzes the first step of heme degradation. Furthermore, they produce biliverdin which acts as the functional chromophore for phytochrome. AlphaFold-modeling in conjunction with docking simulations showed that HoxB may not function as a heme oxygenase despite its observed impact on red-light sensing. Instead, HoxB appeared to more closely resemble a largely uncharacterized family of proteins somewhat resembling TenA-E of A. thaliana by potentially binding amino-pyrimidine compounds and forming homotetramers. The protein localized in the cytoplasm and in nuclei in a manner dependent on the developmental regulator VeA. Deletion of hoxB reduced hyphal growth when grown on meadia containing peroxides, menadione and paraquat. This mutant phenotype was rescued by re-complementation of the mutant with a wildtype hoxB gene. Furthermore, the hoxB-deletion strain showed an abnormally large increase in intracellular reactive oxygen species upon illumination with blue light and failed to express oxidative stress genes like catalase upon induction with hydrogen peroxide. ... mehrInterestingly, HoxB interacted with the cryptochrome CryA in nuclei and mutants of CryA and VeA partially mimicked the growth and transcriptional phenotypes displayed by hoxB-deletion and overexpression. Genome-wide expression comparison of wild type A. nidulans and a hoxB-mutant strain revealed a small set of genes relating to combating oxidative stress such as catalase, thioredoxin, peroxidases and bilirubin and glutathione transporters in response to hydrogen peroxide. While the exact mode of action by which HoxB facilitates these changes requires further investigation, it is feasible that HoxB it functions as a peroxide detector through cysteine oxidation and disulfide bond-formation in the cytoplasm and in nuclei. Additionally, in the presence of oxidative stress, HoxB may act as a negative regulator of CryA to derepress the stress-related transcription factor AtfA. In the absence of oxidative stress HoxB may disengage and CryA may downregulate AtfA to prevent the expression of genes relating to combatting oxidative stress.