The UPC2 gene in Kluyveromyces lactis stress adaptation
Language English Country United States Media print-electronic
Document type Journal Article
Grant support
APVV-19-0094
Agentúra na Podporu Výskumu a Vývoja
VEGA 1/0697/18
Agentúra Ministerstva Školstva, Vedy, Výskumu a Športu SR
VEGA 1/0388/22
Agentúra Ministerstva Školstva, Vedy, Výskumu a Športu SR
UK/62/2021
Univerzita Komenského v Bratislave
PubMed
35352326
DOI
10.1007/s12223-022-00968-3
PII: 10.1007/s12223-022-00968-3
Knihovny.cz E-resources
- Keywords
- Ergosterol, Kluyveromyces lactis, Lipid trafficking, Oxidative stress, Susceptibility, UPC2,
- MeSH
- Gene Deletion MeSH
- Ergosterol metabolism MeSH
- Fungal Proteins * genetics metabolism MeSH
- Kluyveromyces * genetics metabolism MeSH
- Gene Expression Regulation, Fungal MeSH
- Transcription Factors genetics metabolism MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Ergosterol MeSH
- Fungal Proteins * MeSH
- Transcription Factors MeSH
KlUpc2p, a transcription factor belonging to the fungal binuclear cluster family, is an important regulator of ergosterol biosynthesis and azole drug resistance in Kluyveromyces lactis. In this work, we show that the absence of KlUpc2p generates Rag- phenotype and modulates the K. lactis susceptibility to oxidants and calcofuor white. The KlUPC2 deletion leads to increased expression of KlMGA2 gene, encoding an important regulator of hypoxic and lipid biosynthetic genes in K. lactis and also KlHOG1 gene. The absence of KlUpc2p does not lead to statistically significant changes in glycerol, corroborating the expression of KlGPD1 gene, encoding NAD+-dependent glycerol-3-phosphate dehydrogenase, that is similar in both the deletion mutant and the parental wild-type strain. Increased sensitivity of Klupc2 mutant cells to brefeldin A accompanied with significant increase in KlARF2 gene expression point to the involvement of KlUpc2p in intracellular signaling. Our observations highlight the connections between ergosterol and fatty acid metabolism to modulate membrane properties and point to the possible involvement of KlUpc2p in K. lactis oxidative stress response.
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Babst M (2020) Regulation of nutrient transporters by metabolic and environmental stresses. Curr Opin Cell Biol 65:35–41 DOI
Bao WG, Guiard B, Fang ZA et al (2008) Oxygen-dependent transcriptional regulator Hap1p limits glucose uptake by repressing the expression of the major glucose transporter gene RAG1 in Kluyveromyces lactis. Eukaryot Cell 7(11):1895–1905 DOI
Becerra M, Tarrio N, González-Siso MI et al (2004) Genome-wide analysis of Kluyveromyces lactis in wild-type and rag2 mtant strains. Genome 47:970–978 DOI
Breunig KD, Bolotin-Fukuhara M, Bianchi MM et al (2000) Regulation of primary carbon metabolism in Kluyveromyces lactis. Enzyme Microb Technol 26:771–780 DOI
Burr R, Espenshade PJ (2018) Oxygen-responsive transcriptional regulation of lipid homeostasis in fungi: Implications for anti-fungal drug development. Semin Cell Dev Biol 81:110–120 DOI
Bussereau F, Casaregola S, Lafay JF et al (2006) The Kluyveromyces lactis repertoire of transcriptional regulators. FEMS Yeast Res 6(3):325–335 DOI
Camponeschi I, Montanari A, Beccaccioli M et al (2021) Light-stress response mediated by the transcription factor KlMga2 in the yeast Kluyveromyces lactis. Front Microbiol 14(12):705012 DOI
Chen XJ, Clark-Walker GD (1999) α- and β-subunits of F1-ATPase are required for survival of petite mutants in Saccharomyces cerevisiae. Mol Gen Genet 262:898–908 DOI
Cialfi S, Uccelletti D, Carducci A et al (2011) KlHsl1 is a component of glycerol response pathways in the milk yeast Kluyveromyces lactis. Microbiology 157:1509–1518 DOI
Davies BSJ, Rine J (2006) A role for sterol levels in oxygen sensing in Saccharomyces cerevisiae. Genetics 174(1):191–201 DOI
García-Rodriguez LJ, Duran A, Roncero C (2000) Calcofluor antifungal action depends on chitin and a functional high-osmolarity glycerol response (HOG) pathway: evidence for a physiological role of the Saccharomyces cerevisiae HOG pathway under noninducing conditions. J Bacteriol 182(9):2428–2437 DOI
González-Siso MI, Garcia-Leiro A, Tarrio N et al (2009) Sugar metabolism, redox balance and oxidative stress response in the respiratory yeast Kluyveromyces lactis. Microb Cell Factories 8:1–17 DOI
Grant CM (2008) Metabolic reconfiguration is a regulated response to oxidative stress. J Biol 7:1–4 DOI
Guida A, Lindstadt C, Maguire SL et al (2011) Using RNA-seq to determine the transcriptional landscape and the hypoxic response of the pathogenic yeast Candida parapsilosis. BMC Genom 12:628 DOI
Jorda T, Puig S (2020) Regulation of ergosterol biosynthesis in Saccharomyces cerevisiae. Genes 11(7):795 DOI
Kiers J, Zeeman AM, Luttik M et al (1998) Regulation of alcoholic fermentation in batch and chemostat cultures of Kluyveromyces lactis CBS 2359. Yeast 14:459–469 DOI
Konecna A, Toth Hervay N, Bencova A et al (2018) Erg6 gene is essential for stress adaptation in Kluyveromyces lactis. FEMS Microbiol Lett. https://doi.org/10.1093/femsle/fny265 PubMed DOI
Konecna A, Toth Hervay N, Valachovic M et al (2016) ERG6 gene deletion modifies Kluyveromyces lactis susceptibility to various growth inhibitors. Yeast 33(12):621–632 DOI
Kooistra R, Hooykaas PJ, Steensma HY (2004) Efficient gene targeting in Kluyveromyces lactis. Yeast 21:781–792 DOI
Labbaoui H, Bogliolo S, Ghugtyal V et al (2017) Role of Arf GTPases in fungal morphogenesis and virulence. PLoS Pathog 13(2):e1006205 DOI
MacPherson S, Larochelle M, Turcotte B et al (2006) A fungal family of transcriptional regulators: the zinc cluster proteins. Microbiol Mol Biol Rev 70(3):583–604 DOI
Micolonghi C, Ottaviano D, Silvio ED et al (2012) A dual signalling pathway for the hypoxic expression of lipid genes, dependent on the glucose sensor Rag4, is revealed by the analysis of the KlMGA2 gene in Kluyveromyces lactis. Microbiology 158:1734–1744 DOI
Mojardín L, Vega M, Moreno F et al (2018) Lack of the NAD DOI
Moye-Rowley WS (2020) Linkage between genes involved in azole resistance and ergosterol biosynthesis. PLoS Pathog 16(9):e1008819 DOI
Ottaviano D, Montanari A, DeAngelis L et al (2015) Unsaturated fatty acids-dependent linkage between respiration and fermentation revealed by deletion of hypoxic regulatory KlMGA2 gene in the facultative anaerobe-respiratory yeast Kluyveromyces lactis. FEMS Yeast Res 15:fov028. https://doi.org/10.1093/femsyr/fov028 PubMed DOI
Rodicio R, Heinisch JJ (2013) Yeast on the milky way: genetics, physiology and biotechnology of Kluyveromyces lactis. Yeast 30:165–177 DOI
Rolland S, Hnatova M, Lamaire M et al (2006) Connection between the Rag4 glucose sensor and the KlRgt1 repressor in Kluyveromyces lactis. Genetics 174:617–626 DOI
Roncero C (2002) The genetic complexity of chitin synthesis in fungi. Curr Genet 41:367–378 DOI
Santomartino R, Camponeschi I, Polo G et al (2019) The hypoxic transcription factor KlMga2 mediates the response to oxidative stress and influences longevity in the yeast Kluyveromyces lactis. FEMS Yeast Res 19(3):foz020. https://doi.org/10.1093/femsyr/foz020 PubMed DOI
Snoek IS, Steensma HY (2006) Why does Kluyveromyces lactis not grow under anaerobic conditions? Comparison of essential anaerobic genes of Saccharomyces cerevisiae with the Kluyveromyces lactis genome. FEMS Yeast Res 6:393–403 DOI
Suchodolski J, Krasowska A (2019) Plasma membrane potential of Candida albicans measured by Di-4-ANEPPS fluorescence depends on growth phase and regulatory factors. Microorganisms 7(4):110 DOI
Suda Y, Kurokawa K, Nakano A (2018) Regulation of ER-Golgi transport dynamics by GTPases in budding yeast. Front Cell Dev Biol 5:122 DOI
Tanigawa M, Kihara A, Terashima M et al (2012) Sphingolipids regulate the yeast high osmolarity glycerol response pathway. Mol Cell Biol 32:2861–2870 DOI
Torres AM, Maceiras ML, Belmonte ER et al (2012) KlRox1p contributes to yeast resistance to metals and is necessary for KlYCF1 expression in the presence of cadmium. Gene 497(1):27–37 DOI
Toth Hervay N, Bencova A, Valachovic M et al (2020) UPC2 gene deletion modifies sterol homeostasis and susceptibility to metabolic inhibitors in Kluyveromyces lactis. Yeast 37:647–657 DOI
Vik A, Rine J (2001) Upc2p and Ecm22p, dual regulators of sterol biosynthesis in Saccharomyces cerevisiae. Mol Cell Biol 21:6395–6405 DOI
Vu BG, Thomas GH, Moye-Rowley WS (2019) Evidence that ergosterol biosynthesis modulates activity of the Pdr1 transcription factor in Candida glabrata. Mbio 10(3):e00934-e1019 DOI
Wilcox LJ, Balderes DA, Wharton B et al (2002) Transcriptional profiling identifies two membrs of the ATP-binding cassette transporter superfamily required for sterol uptake in yeast. J Biol Chem 277:32466–32472 DOI