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http://dx.doi.org/10.4014/jmb.2004.04041

Involvement of Mrs3/4 in Mitochondrial Iron Transport and Metabolism in Cryptococcus neoformans  

Choi, Yoojeong (Department of Systems Biotechnology, Chung-Ang University)
Do, Eunsoo (Department of Systems Biotechnology, Chung-Ang University)
Hu, Guanggan (The Michael Smith Laboratories, Department of Microbiology and Immunology, University of British Columbia)
Caza, Melissa (The Michael Smith Laboratories, Department of Microbiology and Immunology, University of British Columbia)
Horianopoulos, Linda C. (The Michael Smith Laboratories, Department of Microbiology and Immunology, University of British Columbia)
Kronstad, James W. (The Michael Smith Laboratories, Department of Microbiology and Immunology, University of British Columbia)
Jung, Won Hee (Department of Systems Biotechnology, Chung-Ang University)
Publication Information
Journal of Microbiology and Biotechnology / v.30, no.8, 2020 , pp. 1142-1148 More about this Journal
Abstract
Mitochondria play a vital role in iron uptake and metabolism in pathogenic fungi, and also influence virulence and drug tolerance. However, the regulation of iron transport within the mitochondria of Cryptococcus neoformans, a causative agent of fungal meningoencephalitis in immunocompromised individuals, remains largely uncharacterized. In this study, we identified and functionally characterized Mrs3/4, a homolog of the Saccharomyces cerevisiae mitochondrial iron transporter, in C. neoformans var. grubii. A strain expressing an Mrs3/4-GFP fusion protein was generated, and the mitochondrial localization of the fusion protein was confirmed. Moreover, a mutant lacking the MRS3/4 gene was constructed; this mutant displayed significantly reduced mitochondrial iron and cellular heme accumulation. In addition, impaired mitochondrial iron-sulfur cluster metabolism and altered expression of genes required for iron uptake at the plasma membrane were observed in the mrs3/4 mutant, suggesting that Mrs3/4 is involved in iron import and metabolism in the mitochondria of C. neoformans. Using a murine model of cryptococcosis, we demonstrated that an mrs3/4 mutant is defective in survival and virulence. Taken together, our study suggests that Mrs3/4 is responsible for iron import in mitochondria and reveals a link between mitochondrial iron metabolism and the virulence of C. neoformans.
Keywords
Cryptococcus neoformans; iron; iron transport; mitochondria; Mrs3/4;
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