Involvement of Mrs3/4 in Mitochondrial Iron Transport and Metabolism in Cryptococcus neoformans
- Authors
- Choi, Y.; Do, E.; Hu, G.; Caza, M.; Horianopoulos, L.C.; Kronstad, J.W.; Jung, W.H.
- Issue Date
- Aug-2020
- Publisher
- NLM (Medline)
- Keywords
- Cryptococcus neoformans; iron; iron transport; mitochondria; Mrs3/4
- Citation
- Journal of microbiology and biotechnology, v.30, no.8, pp 1142 - 1148
- Pages
- 7
- Journal Title
- Journal of microbiology and biotechnology
- Volume
- 30
- Number
- 8
- Start Page
- 1142
- End Page
- 1148
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/53631
- DOI
- 10.4014/jmb.2004.04041
- ISSN
- 1017-7825
1738-8872
- 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.
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Collections - College of Biotechnology & Natural Resource > Department of Systems Biotechnology > 1. Journal Articles
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