The regulatory proteins Rtg1/3 govern sphingolipid homeostasis in the human-associated yeast Candida albicans
Open accessAbstract
Integrating nutrient sensing with the synthesis of complex molecules is a central feature of metabolism. Yet the regulatory mechanisms underlying such integration are often unknown. Here, we establish that the transcription regulators Rtg1/3 are key determinants of sphingolipid homeostasis in the human fungal pathogen Candida albicans. Quantitative analysis of the C. albicans lipidome reveals Rtg1/3-dependent alterations in all complex sphingolipids and their precursors, ceramides. Mutations in the regulators render the fungus susceptible to myriocin, a sphingolipid synthesis inhibitor. Rtg1/3 exert control on the expression of several enzymes involved in the synthesis of sphingolipids' building blocks, and the regulators are activated upon engulfment of C. albicans cells by human neutrophils. We demonstrate that Rtg1p and Rtg3p are regulated at two levels, one in response to sphingolipids and the other by the nutrient sensor TOR. Our findings, therefore, indicate that the Rtg1/3 system integrates nutrient sensing into the synthesis of complex lipids.
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CaRtg1 and CaRtg3 are involved in sphingolipid homeostasis and adaptation to commensalism and pathogenicity.
“CaRtg1 and CaRtg3 were also shown to be involved in sphingolipid homeostasis (Moreno-Velásquez et al. 2020), and adaptation to commensalism and pathogenicity (Pérez et al. 2013).”
From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Moreno-Velásquez et al. 2020
Rtg transcription factors, together with Hms1 and Tye7, were shown to be a key part of a regulatory circuit controlling diverse metabolic processes related to commensalism and pathogenicity, as well as sphingolipid homeostasis.
“Together with several other transcription factors, such as Hms1 and Tye7, they were shown to be a key part of a regulatory circuit that controls diverse metabolic processes related to multiple aspects of commensalism and pathogenicity (Pérez et al. 2013), as well as the sphingolipid homeostasis (Moreno-Velásquez et al. 2020).”
From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Moreno-Velásquez et al. 2020
Under all conditions tested, homozygous deletion of either RTG1 or RTG3 impaired growth to the same extent as homozygous deletion of both genes, consistent with their protein products functioning together as a complex.
“Under all conditions tested, homozygous deletion of either RTG1 or RTG3 impaired growth to the same extent as homozygous deletion of both genes, consistent with their protein products functioning together as a complex32,33.”
From Multifactor transcriptional control of alternative oxidase induction integrates diverse environmental inputs to enable fungal virulence (2023) · cites this paper as [33]
In C. albicans, the Rtg1/Rtg3 complex has been implicated in regulating the expression of genes involved in multiple metabolic and signaling pathways.
“In C. albicans, the Rtg1/Rtg3 complex has been implicated in regulating the expression of genes involved in multiple metabolic and signaling pathways32,33.”
From Multifactor transcriptional control of alternative oxidase induction integrates diverse environmental inputs to enable fungal virulence (2023) · cites this paper as [33]
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References 55 · Cited by 25
- Authors
- Moreno-Velásquez, S. D., Tint, S. H., del Olmo Toledo, V., Torsin, S., De, S., & Pérez, J. C.
- Affiliations
- University of Würzburg (DE)
- Universitätsklinikum Würzburg (DE)
- Corresponding author
- Pérez, J. Christian
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 30
- Issue
- 3
- Pages
- 620-629.e6
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W3003111286
- Cited by
- 25
- References
- 55
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 3 · 2023: 6 · 2022: 1 · 2021: 5 · 2020: 1
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Deutsche Forschungsgemeinschaft (PE 2371/2-1)
- Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg (A-296)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- Candida albicans, sphingolipid homeostasis, ceramide synthesis, myriocin, transcriptional regulation, lipidome, fungal pathogens
- MeSH terms
- Adult, Candida albicans, Cell Nucleus, Fungal Proteins, Homeostasis, Humans, Mutation, Neutrophils, Phenotype, Phosphorylation, RNA, Messenger, Sphingolipids, Subcellular Fractions, Signal Transduction, Gene Expression Regulation, Fungal, Gene Expression Profiling, Metabolomics, Proteolysis
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