Iron homeostasis playscritical roles in respiration, DNA synthesis and repair, ribosome biogenesis, metabolism and other cellular processes in all organisms. The defects in iron uptake lead to decreased virulence in pathogenic fungi.
However, excess iron generatestoxic reactive oxygen species (ROS) through Fenton’s reaction resulting in damage to cellular components. All organisms have developed tightly homeostatic regulatory mechanisms to balance uptake, consumption and storage of iron. However, the study on regulation of iron balance in plant pathogenic fungi has not been well characterized. The Fusarium research team led by Dr. Zhonghua Ma in the Institute of Biotechnology, Zhejiang University has discovered a novel regulatory mechanism of ABC protein Atm1 in iron homeostasis. They reported their findings in the journal of PLoS Pathogens on September 23 as a cover story.
In recent years, due to climate change, large-scale wheat-corn rotation and straw returning, the FHB caused by fungal pathogen F. graminearum has been aggravated in China, which seriously affects the yield of wheat production. In addition, mycotoxins deoxynivalenol (DON) and its derivatives, produced by F. graminearum in infested grains, represent a serious threat to human and animal health. The Fusarium research team found that one ABC transporter (named FgAtm1) is involved in regulating iron homeostasis, by screening sensitivity to iron stress for 60 ABC transporter mutants of F. graminearum. The lack of FgAtm1 reduces the activity of cytosolic Fe-S proteins nitrite reductase and xanthine dehydrogenase, which causes high expression of FgHapX via activating transcription factor FgAreA. FgHapX represses transcription of genes for iron-consuming proteins directly but activates genes for iron acquisition proteins by suppressing another iron regulator FgSreA. Taken together, this study uncovers a novel regulatory mechanism of iron homeostasis mediated by an ABC transporter in an important pathogenic fungus.
Dr. Zhihui Wang is the first author of this article. Prof. Ma Zhonghua and Prof. Yin Yanni are the co-corresponding authors. This research was supported by the National Natural Science Fund for Distinguished Young Scholar, the National Key R&D Program of China, China Agriculture Research System.
Related Links: https://doi.org/10.1371/journal.ppat.1007791
Cover
As a mitochondrial ABC transporter in Fusarium graminearum, FgAtm1 regulates the activity of cytosolic Fe-S proteins via transporting GSH-linked [2Fe-2S] clusters from mitochondria into cytoplasm. The lack of FgAtm1 reduces the activity of cytosolic Fe-S proteins nitrite reductase and xanthine dehydrogenase, which causes high expression of iron regulator FgHapX via activating the transcription factor FgAreA. FgHapX represses transcription of the genes for iron-consuming proteins, but activates the genes for iron-acquisition proteins. The image indicates that the growth of ΔFgAtm1 is accelerated by feeding with each of the final catalytic products of cytosolic Fe-S proteins. Wang et al.