Proteomic profiling of the monothiol glutaredoxin Grx3 reveals its global role in the regulation of iron dependent processes

English version

Autoři: Selma S. Alkafeef ^aff001; Shelley Lane ^aff001; Clinton Yu ^aff003; Tingting Zhou ^aff001; Norma V. Solis ^aff004; Scott G. Filler ^aff004; Lan Huang ^aff003; Haoping Liu ^aff001
Působiště autorů: Department of Biological Chemistry, University of California, Irvine, California, United States of America ^aff001; Department of Biochemistry, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait ^aff002; Department of Physiology & Biophysics, University of California, Irvine, California, United States of America ^aff003; Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States of America ^aff004; David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America ^aff005
Vyšlo v časopise: Proteomic profiling of the monothiol glutaredoxin Grx3 reveals its global role in the regulation of iron dependent processes. PLoS Genet 16(6): e32767. doi:10.1371/journal.pgen.1008881
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008881

Souhrn

Iron is an essential nutrient required as a cofactor for many biological processes. As a fungal commensal-pathogen of humans, Candida albicans encounters a range of bioavailable iron levels in the human host and maintains homeostasis with a conserved regulatory circuit. How C. albicans senses and responds to iron availability is unknown. In model yeasts, regulation of the iron homeostasis circuit requires monothiol glutaredoxins (Grxs), but their functions beyond the regulatory circuit are unclear. Here, we show Grx3 is required for virulence and growth on low iron for C. albicans. To explore the global roles of Grx3, we applied a proteomic approach and performed in vivo cross-linked tandem affinity purification coupled with mass spectrometry. We identified a large number of Grx3 interacting proteins that function in diverse biological processes. This included Fra1 and Bol2/Fra2, which function with Grxs in intracellular iron trafficking in other organisms. Grx3 interacts with and regulates the activity of Sfu1 and Hap43, components of the C. albicans iron regulatory circuit. Unlike the regulatory circuit, which determines expression or repression of target genes in response to iron availability, Grx3 amplifies levels of gene expression or repression. Consistent with the proteomic data, the grx3 mutant is sensitive to heat shock, oxidative, nitrosative, and genotoxic stresses, and shows growth dependence on histidine, leucine, and tryptophan. We suggest Grx3 is a conserved global regulator of iron-dependent processes occurring within the cell.

Klíčová slova:

Biosynthesis – Candida albicans – Gene expression – Homeostasis – Mouse models – Saccharomyces cerevisiae – Transcription factors – Transcriptional control

Zdroje

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