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Cited by 55Mitochondrial Function and PathologyFungal and yeast genetics researchIron Metabolism and Disorders

Candida albicans lacking the frataxin homologue: a relevant yeast model for studying the role of frataxin

Santos, Renata, Buisson, Nicole, Knight, Simon A. B., Dancis, Andrew, Camadro, Jean‐Michel, Lesuisse, Emmanuel·2004·Molecular Microbiology
DOI 10.1111/j.1365-2958.2004.04281.x
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Abstract

Summary: We cloned the CaYFH1 gene that encodes the yeast frataxin homologue in Candida albicans. CaYFH1 was expressed in Δ yfh1 Saccharomyces cerevisiae cells, where it compensated for all the phenotypes tested except for the lack of cytochromes. Double Δ Cayfh1/Δ Cayfh1 mutant had severe defective growth, accumulated iron in their mitochondria, lacked aconitase and succinate dehydrogenase activity and had defective respiration. The reductive, siderophore and haem uptake systems were constitutively induced and the cells excreted flavins, thus behaving like iron‐deprived wild‐type cells. Mutant cells accumulated reactive oxygen species and were hypersensitive to oxidative stress, but not to iron. Cytochromes were less abundant in mutants than in wild‐type cells, but this did not result from defective haem synthesis. The low cytochrome concentration in mutant cells was comparable to that of iron‐deprived wild‐type cells. Mitochondrial iron was still available for haem synthesis in Δ Cayfh1/Δ Cayfh1 cells, in contrast to S. cerevisae Δ yfh1 cells. CaYFH1 transcription was strongly induced by iron, which is consistent with a role of CaYfh1 in iron storage. Iron also regulated transcription of CaHEM14 (encoding protoporphyrinogen oxidase) but not that of CaHEM15 (encoding ferrochelatase). There are thus profound differences between S. cerevisiae and C. albicans in terms of haem synthesis, cytochrome turnover and the role of frataxin in these processes.

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Crossref · 10.1111/j.1365-2958.2004.04281.x

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  • Category 2 contained 31 mutants with general growth defects that were independent of iron supplementation.

    “Category 2 contained another 31 mutants with general growth defects that were independent of iron supplementation (Fig. 1b), including deletions of known and iron-associated genes (YFH1, ATM1) conserved in most fungi such as C. albicans (28, 29) and S. cerevisiae (30, 31).”

    From A novel hybrid iron regulation network combines features from pathogenic and nonpathogenic yeasts (2016) · cites this paper as [28]

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Authors
Santos, R., Buisson, N., Knight, S. A. B., Dancis, A., Camadro, J., & Lesuisse, E.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • University of Pennsylvania (US)
Corresponding author
Lesuisse, Emmanuel
ORCID
Venue
Molecular Microbiology
Publisher
Wiley
Published
2004-09-06
Volume
54
Issue
2
Pages
507-519
ISSN
  • 0950-382X (ISSN-L)
  • 1365-2958
DOI
10.1111/j.1365-2958.2004.04281.x
OpenAlex
W1597070962
Cited by
55
References
57
Citations by year
2026: 1 · 2023: 3 · 2020: 3 · 2019: 3 · 2018: 4 · 2017: 1 · 2016: 1 · 2014: 2 · 2013: 2 · 2012: 3
FWCI
1.54
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Molecular Microbiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Association pour la Recherche sur le Cancer
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK 53953)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Keywords
Candida albicans, frataxin, mitochondrial iron accumulation, haem synthesis, cytochrome synthesis, aconitase, succinate dehydrogenase, oxidative stress, reactive oxygen species, protoporphyrinogen oxidase, ferrochelatase, yeast model
MeSH terms
Frataxin, Candida albicans, Friedreich Ataxia, Fungal Proteins, Genetic Complementation Test, Heme, Humans, Iron, Mitochondria, Porphyrins, Saccharomyces cerevisiae, Gene Expression Regulation, Fungal, Reactive Oxygen Species, Oxidative Stress, Cell Respiration, Iron-Binding Proteins

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