A fungal ABC transporter FgAtm1 regulates iron homeostasis via the transcription factor cascade FgAreA-HapX

• Published in: PLoS pathogens Vol. 15; no. 9; p. e1007791
• Main Authors: Wang, Zhihui, Ma, Tianling, Huang, Yunyan, Wang, Jing, Chen, Yun, Kistler, H Corby, Ma, Zhonghua, Yin, Yanni
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.09.2019; Public Library of Science (PLoS)
• Subjects: ABC transporter; ABC transporters; Analysis; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Base Sequence; Biology and Life Sciences; Biosynthesis; Biotechnology; Cereal crops; Diabetic retinopathy; DNA, Fungal - genetics; Edible Grain - microbiology; Eukaryotes; Fungal Proteins - genetics; Fungal Proteins - metabolism; Fungi; Fusarium - genetics; Fusarium - metabolism; Fusarium - pathogenicity; Fusarium graminearum; Gene Deletion; Genes; Genes, Fungal; Glutaredoxin; Homeostasis; Iron; Iron (Nutrient); Iron - metabolism; Iron-sulfur proteins; Iron-Sulfur Proteins - genetics; Iron-Sulfur Proteins - metabolism; Kinases; Laboratories; Medicine and Health Sciences; Metabolism; Models, Biological; Molecular biology; Mutants; Mutation; Nitrite reductase; Novels; Phosphorylation; Physiological aspects; Plant Diseases - microbiology; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Protein-serine/threonine kinase; Proteins; Psychics; Purines; Reductases; Regulatory mechanisms (biology); Research and Analysis Methods; Rice; Siderophores - genetics; Siderophores - metabolism; Stress, Physiological; Structure; Sulfur; Transcription factors; Transport proteins; Transporter; Xanthine; Xanthine dehydrogenase; China; United States > US
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1007791

Iron homeostasis is important for growth, reproduction and other metabolic processes in all eukaryotes. However, the functions of ATP-binding cassette (ABC) transporters in iron homeostasis are largely unknown. Here, we 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 Fusarium graminearum, a devastating fungal pathogen of small grain cereal crops worldwide. 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. In addition, the transcriptional activity of FgHapX is regulated by the monothiol glutaredoxin FgGrx4. Furthermore, the phosphorylation of FgHapX, mediated by the Ser/Thr kinase FgYak1, is required for its functions in iron homeostasis. Taken together, this study uncovers a novel regulatory mechanism of iron homeostasis mediated by an ABC transporter in an important pathogenic fungus.