Research interests
Barth syndrome disease
Barth syndrome (BTHS) is a hereditary mitochondrial disorder characterized by a reduction in total cardiolipin and the accumulation of its precursor, monolysocardiolipin, resulting from the deficiency of the transacylase enzyme tafazzin. However, the molecular mechanisms underlying BTHS pathology remain inadequately understood. In our group, we characterized the double mutant pgc1Δtaz1Δ in Saccharomyces cerevisiae, lacking phosphatidylglycerol-specific phospholipase C and tafazzin, as a novel yeast model for BTHS. In contrast to the previously utilized taz1Δ mutant, this model exhibits an accumulation of phosphatidylglycerol, more closely mirroring the characteristics of human BTHS cells. Overall, our results show that the pgc1Δtaz1Δ mutant better mimics the cellular phenotype of BTHS patients than taz1Δ cells, both in terms of lipid composition and the degree of disruption of mitochondrial structure and function. This favors the new model for use in future studies.
Attenuation of inflammation
Recognition of microbial infection and initiation of host defense responses is regulated by multiple mechanisms. One of the best-studied pattern recognition receptors is Toll-like receptor 4 (TLR4), a receptor for bacterial lipopolysaccharide (LPS). New discoveries identified high-affinity inhibitory interactions between lung surfactant anionic phospholipids and TLR2, TLR4, respiratory syncytial virus (RSV), and influenza A virus (IAV) suggest that anionic phospholipids play an important role in the regulation of both infectious and innate immune processes. In the project, we would like to use the fact that phosphatidylglycerol (PG) is a strong antiviral and antibacterial agent. Our goal is to influence the immune response and increase the synthesis of PG directly in cells by the action of a specific drug that would affect the regulation of PG biosynthetic pathways. Administration of a drug capable of increasing PG synthesis in individuals could effectively prevent LPS activation of TLR4 or attachment of the virus to cellular epithelium and significantly reduce the immune response and transmission of infectious particles.
Mitochondrial communication
In eukaryotic cells, mitochondria are constantly adapting to changes in the biological activity of the cell, i.e., changes in nutrient availability and environmental stresses. We propose a model in which this adaptation is mediated by lipids. Specifically, we show that mitochondrial phospholipids regulate the biosynthesis of cellular sphingolipids and vice versa. To do this, lipids move by free diffusion, which does not require energy and works under any condition. This model represents a simple way for the cell to coordinate mitochondrial structure and performance with the actual needs of overall cellular metabolism. Its simplicity makes it a universally applicable principle of cellular regulation.
People
Mgr. Mária Balážová, PhD. – vedúca skupiny
RNDr. Lenka Bábelová, PhD.
Mgr. Ivana Ďurišová – doktorandka
Mgr. Ingrid Zriniová – doktorandka
Selected publications
- BALÁŽOVÁ, Mária – VESELÁ, Petra – BÁBELOVÁ, Lenka – ĎURIŠOVÁ, Ivana – KÁŇOVIČOVÁ, Paulína – ZAHUMENSKÝ, Jakub – MALÍNSKÝ, Ján. Two Different Phospholipases C, Isc1 and Pgc1, Cooperate To Regulate Mitochondrial Function. In Microbiology Spectrum, 2022, vol. 10, no. 6, e02489-22. ISSN 2165-0497.
- KÁŇOVIČOVÁ, Paulína – ČERMÁKOVÁ, Petra – KUBALOVÁ, Dominika – BÁBELOVÁ, Lenka – VESELÁ, Petra – VALACHOVIČ, Martin – ZAHUMENSKÝ, Jakub – HORVÁTH, Anton – MALÍNSKÝ, Ján – BALÁŽOVÁ, Mária. Blocking phosphatidylglycerol degradation in yeast defective in cardiolipin remodeling results in a new model of the Barth syndrome cellular phenotype. In Journal of Biological Chemistry, 2022, vol. 298, no. 1, art. no. 101462. ISSN 0021-9258.
- VAŠKOVIČOVÁ, Katarína – VESELÁ, Petra – ZAHUMENSKÝ, Jakub – FOLKOVÁ, Dagmar – BALÁŽOVÁ, Mária – MALÍNSKÝ, Ján. Plasma Membrane Protein Nce102 Modulates Morphology and Function of the Yeast Vacuole. In Biomolecules : Open Access Journal, 2020, vol. 10, no. 11, art. no. 1476. ISSN 2218-273X.
- KUBALOVÁ, Dominika – KÁŇOVIČOVÁ, Paulína – VESELÁ, Petra – AWADOVÁ, Thuraya – DŽUGASOVÁ, Vladimíra – DAUM, G, – MALÍNSKÝ, Ján – BALÁŽOVÁ, Mária. The lipid droplet protein Pgc1 controls the subcellular distribution of phosphatidylglycerol. In FEMS Yeast Research, 2019, vol. 19, iss. 5, art. no. foz045. ISSN 1567-1356.
- VAŠKOVIČOVÁ, Katarína – AWADOVÁ, Thuraya – VESELÁ, Petra – BALÁŽOVÁ, Mária – OPEKAROVÁ, Miroslava – MALÍNSKÝ, Ján. mRNA decay is regulated via sequestration of the conserved 5′-3′ exoribonuclease Xrn1 at eisosome in yeast. In European Journal of Cell Biology, 2017, vol. 96, no. 6, p. 591-599. ISSN 0171-9335.
- POKORNÁ, Lucia – ČERMÁKOVÁ, Petra – HORVÁTH, Anton – BAILE M. G., M. G. – CLAYPOOL S. M., S. M. – GRIAČ, Peter – MALÍNSKÝ, Ján – BALÁŽOVÁ, Mária. Specific degradation of phosphatidylglycerol is necessary for proper mitochondrial morphology and function. In Biochimica et Biophysica Acta : bioenergetics, 2016, vol. 1857, p. 34-45. ISSN 0005-2728.
- ŠIMOČKOVÁ, Mária – HOLIČ, Roman – TAHOTNÁ, Dana – PATTON-VOGT, Jana – GRIAČ, Peter. Yeast Pgc1p (YPL206c) Controls the Amount of Phosphatidylglycerol via a Phospholipase C-type Degradation Mechanism. In Journal of Biological Chemistry, 2008, vol. 283, no. 25, p. 17107-17115. ISSN 0021-9258.