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Updated: May 20, 2026

Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
Identification and functional characterization of mitochondrial carrier Mrs4 in Candida albicans
Ning Xu1, Xinxin Cheng, Qilin Yu
1Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Department of Microbiology, Nankai University, Tianjin, China.
Abstract:
Iron is an essential nutrient required for the growth and metabolism in Candida albicans. Here, we for the first time identified Mrs4 as a new member of mitochondrial carrier family in C. albicans. Our experiments revealed that C. albicans Mrs4 (CaMrs4) is localized to the mitochondria and required for mitochondrial morphology. We found that CaMrs4 is required for cell growth, and the mrs4Δ/Δ mutant showed a more severe growth defect in iron deficiency. Deletion of MRS4 affected cellular iron content by altering the expression of iron regulon genes in C. albicans, such as AFT2, SMF3, FTR1 and ISU1. Candida albicans Aft2 factor functions as a negative regulator of MRS4 expression through the CACCC Aft-type sequence in a gene dose-dependent fashion. In addition, the mrs4Δ/Δ mutant exhibited hypersensitivity to oxidants and most metal ions, but decreased sensitivity to cobalt. Exogenous iron could suppress the sensitivity of the mrs4Δ/Δ mutant to oxidants and most metal ions, suggesting that the role of CaMrs4 is partially mediated by iron availability. Furthermore, deletion of MRS4 resulted in delayed filamentation under tested conditions. Taken together, these findings characterize a new mitochondrial carrier and provide a novel insight into the role of CaMrs4 in mitochondrial function.
Insights
This study identifies Mrs4 as a novel mitochondrial carrier in Candida albicans, crucial for cell growth, mitochondrial structure, and iron homeostasis. Its absence impacts iron regulon genes and filamentation, highlighting its role in fungal iron metabolism.
Area of Science:
- Mycology
- Cell Biology
- Biochemistry
Background:
- Iron is vital for Candida albicans growth and metabolism.
- Mitochondrial carriers play critical roles in cellular transport and function.
- Understanding novel mitochondrial proteins is key to deciphering fungal physiology.
Purpose of the Study:
- To identify and characterize a new member of the mitochondrial carrier family in Candida albicans.
- To elucidate the function of CaMrs4 in mitochondrial morphology, cell growth, and iron metabolism.
- To investigate the regulatory relationship between CaMrs4 and the Aft2 transcription factor.
Main Methods:
- Gene deletion to create the mrs4Δ/Δ mutant.
- Mitochondrial localization studies using CaMrs4.
- Analysis of gene expression for iron regulon genes (AFT2, SMF3, FTR1, ISU1).
- Phenotypic analysis including growth assays, oxidant sensitivity, and filamentation tests.
Main Results:
- CaMrs4 is localized to mitochondria and essential for mitochondrial morphology and cell growth.
- The mrs4Δ/Δ mutant exhibits severe growth defects under iron deficiency and altered expression of iron regulon genes.
- CaMrs4 deletion leads to hypersensitivity to oxidants and metal ions, with iron supplementation partially rescuing these phenotypes.
- MRS4 deletion results in delayed filamentation in Candida albicans.
Conclusions:
- CaMrs4 is a novel mitochondrial carrier involved in iron homeostasis and mitochondrial function in Candida albicans.
- CaMrs4 plays a significant role in regulating cellular iron content and response to oxidative stress.
- The findings provide new insights into the complex mechanisms of iron management and mitochondrial dynamics in pathogenic fungi.
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