Abstract
In the yeast Saccharomyces cerevisiae, neutral lipids can be synthesized by four acyltransferases, namely Dga1p and Lro1p producing triacylglycerols (TAG) and Are1p and Are2p forming steryl esters (SE). TAG and SE are stored in an organelle called lipid particles/droplet. Growth of yeast cells on oleate-supplemented media strongly induced proliferation of lipid particles and specifically the synthesis of TAG, which serve as the major pool for the excess of fatty acids. Surprisingly, SE synthesis was strongly inhibited under these conditions. Here, we show that this effect was not due to decreased expression of ARE2 encoding the major yeast SE synthase at the transcriptional level but to competitive enzymatic inhibition of Are2p by free oleate. Consequently, a triple mutant dga1Deltalro1Deltaare1DeltaARE2(+) grown on oleate did not form substantial amounts of SE and exhibited a growth phenotype similar to the dga1Deltalro1Deltaare1Deltaare2Delta quadruple mutant, including lack of lipid particles. Growth of these mutants on oleate was strongly delayed, and cell viability was decreased but rescued by adaptation. In these strains, oleate stress caused morphological changes of intracellular membranes, altered phospholipid composition and formation of an additional lipid class, ethyl esters of fatty acids. In summary, our data showed that exposure to oleate led to disturbed lipid and membrane homeostasis along with liposensitivity of the yeast.
Highlights
Fatty acids are essential molecules for all types of cells
Are2p esterifies mainly ergosterol, whereas Are1p accepts ergosterol precursors as adequate substrates [16]. These findings are in line with the fact that ergosterol is a major sterol under aerobic conditions, whereas heme-deficient cells are unable of PC, phosphatidylcholine; TM, triple mutant; QM, quadruple mutant; CWW, cell wet weight; GLC, gas-liquid chromatography
We report that strains deficient in TAG or steryl esters (SE) synthesis were able to tolerate high amounts of exogenous free fatty acid especially when adapted to these growth conditions
Summary
Fatty acids are essential molecules for all types of cells. They are required as building blocks for the synthesis of complex lipids and for membrane assembly. Exogenous free fatty acids (FFA) are taken up by the yeast cell and activated to acyl-CoA. These activated fatty acids enter metabolic processes such as -oxidation in the peroxisomes or synthesis of membrane-forming and storage lipids. Are2p is the major SE-synthesizing enzyme under aerobic conditions, whereas Are1p is up-regulated in heme-deficient or anaerobic yeast cells. Are2p esterifies mainly ergosterol, whereas Are1p accepts ergosterol precursors as adequate substrates [16] These findings are in line with the fact that ergosterol is a major sterol under aerobic conditions, whereas heme-deficient cells are unable of PC, phosphatidylcholine; TM, triple mutant; QM, quadruple mutant; CWW, cell wet weight; GLC, gas-liquid chromatography
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