Research interests
Lipid droplets
Lipid droplets are primarily recognized as energy reservoirs and storage sites for membrane lipid components. Our laboratory is interested in lipid droplets’ role as organelles effective in reducing the lipotoxicity of sterols and fatty acids. We study the protective properties of lipid droplets in the unicellular eukaryotic organism Saccharomyces cerevisiae. Under certain conditions, S. cerevisiae and some other fungi import exogenous sterols, which can be perilous. Potentially harmful sterol precursors can accumulate after treatment with antifungal drugs. Understanding lipid droplets as native defense organelles against lipotoxicity will provide an important knowledge for the development of new antifungals.
Utilisation of exogenous sterols
Typically, eukaryotic organisms synthesise their own sterols. However, under some circumstances, they may need to utilise sterols from the environment. Dysregulation of sterol uptake can lead to serious issues for the organism. For instance, in humans, excessive utilisation of cholesterol or defects in the secretion of xenosterols, such as plant sterols, could result in lipid disorders, like atherosclerosis or sitosterolemia. In unicellular organisms, sterol uptake is critical when internal biosynthesis is blocked. We study the fate of imported exogenous sterols in yeast Saccharomyces cerevisiae which has been shown to utilise a wide range of sterols, including animal cholesterol or plant sterols. Importantly, the utilisation of exogenous sterols in some pathogenic fungi has been associated with resistance to antifungals.
Homeostasis of ergosterol metabolism
Given the increasing resistance of microorganisms to antibiotics, it is critical to develop new drugs or improve the currently used ones. In fungi, ergosterol or the ergosterol biosynthesis pathway are targets of the majority of currently used antifungals. We are studying the biosynthesis of ergosterol and its homeostasis in model fungi, yeast Saccharomyces cerevisiae. We are particularly interested in the distribution of ergosterol among the membrane and lipid droplet fractions.
People
Mgr. Martin Valachovič, PhD. – head of the group
Mgr. Zuzana Pevalová, PhD.
Allumni
Mgr. Lívia Petrisková, PhD. – PhD. thesis
Mgr. Marianna Bačinská – Msc. thesis
Mgr. Zuzana Žiaková – Msc. thesis
Selected publications
ELIAŠ, Daniel – TÓTH HERVAY, Nora – JACKO, Juraj – MORVOVÁ, Marcela, Jr. – VALACHOVIČ, Martin – GBELSKÁ, Yvetta. Erg6p is essential for antifungal drug resistance, plasma membrane properties and cell wall integrity in Candida glabrata. In FEMS Yeast Research, 2022, vol. 21, no. 1, art. no. foac045.
BENCOVÁ, Alexandra – GOFFA, Eduard – MORVOVÁ, M. – VALACHOVIČ, Martin – GRIAČ, Peter – TÓTH HERVAY, Nora – GBELSKÁ, Yvetta. The absence of PDR16 gene restricts the overexpression of CaSNQ2 gene in the presence of fluconazole in Candida albicans. In Mycopathologia, 2020, vol. 185, no. 3, p. 455-465.
PÁPAY, Marek – KLEIN, Cornelia – HAPALA, Ivan – PETRISKOVÁ, Lívia – KUCHLER, Karl – VALACHOVIČ, Martin. Mutations in the nucleotide-binding domain of putative sterol importers Aus1 and Pdr11 selectively affect utilization of exogenous sterol species in yeast. In Yeast, 2020, vol. 37, iss. 1, p. 5-14.
CSÁKY, Zsófia – GARAIOVÁ, Martina – KODEDOVÁ, Marie – VALACHOVIČ, Martin – SYCHROVÁ, Hana – HAPALA, Ivan. Squalene lipotoxicity in a lipid droplet-less yeast mutant is linked to plasma membrane dysfunction. In Yeast, 2020, vol. 37, iss. 1, p. 45-62.
VALACHOVIČ, Martin – GARAIOVÁ, Martina – HOLIČ, Roman – HAPALA, Ivan. Squalene is lipotoxic to yeast cells defective in lipid droplet biogenesis. In Biochemical and biophysical research communications, 2016, vol. 469, p. 1123-8.
KOHÚT, Peter – WUSTNER, D. – HRONSKÁ, Lucia – KUCHLER, Karl – HAPALA, Ivan – VALACHOVIČ, Martin. The role of ABC proteins Aus1p and Pdr11p in the uptake of external sterols in yeast: Dehydroergosterol fluorescence study. In Biochemical and biophysical research communications, 2011, vol. 404, no. 1, p. 233-238.