title: Influence of squalene on lipid particle/droplet and membrane organization in the yeast Saccharomyces cerevisiae.
abstract: In a previous study (Spanova et al., 2010, J. Biol. Chem., 285, 6127-6133) we demonstrated that squalene, an intermediate of sterol biosynthesis, accumulates in yeast strains bearing a deletion of the HEM1 gene. In such strains, the vast majority of squalene is stored in lipid particles/droplets together with triacylglycerols and steryl esters. In mutants lacking the ability to form lipid particles, however, substantial amounts of squalene accumulate in organelle membranes. In the present study, we investigated the effect of squalene on biophysical properties of lipid particles and biological membranes and compared these results to artificial membranes. Our experiments showed that squalene together with triacylglycerols forms the fluid core of lipid particles surrounded by only a few steryl ester shells which transform into a fluid phase below growth temperature. In the hem1∆ deletion mutant a slight disordering effect on steryl esters was observed indicated by loss of the high temperature transition. Also in biological membranes from the hem1∆ mutant strain the effect of squalene per se is difficult to pinpoint because multiple effects such as levels of sterols and unsaturated fatty acids contribute to physical membrane properties. Fluorescence spectroscopic studies using endoplasmic reticulum, plasma membrane and artificial membranes revealed that it is not the absolute squalene level in membranes but rather the squalene to sterol ratio which mainly affects membrane fluidity/rigidity. In a fluid membrane environment squalene induces rigidity of the membrane, whereas in rigid membranes there is almost no additive effect of squalene. In summary, our results demonstrate that squalene (i) can be well accommodated in yeast lipid particles and organelle membranes without causing deleterious effects; and (ii) although not being a typical membrane lipid may be regarded as a mild modulator of biophysical membrane properties.
authors.affiliation: Institute of Biochemistry, Graz University of Technology, Graz, Austria.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Spanova
authors.forename: Dagmar
authors.initials: D
authors.lastname: Zweytick
authors.forename: Karl
authors.initials: K
authors.lastname: Lohner
authors.forename: Lisa
authors.initials: L
authors.lastname: Klug
authors.forename: Erich
authors.initials: E
authors.lastname: Leitner
authors.forename: Albin
authors.initials: A
authors.lastname: Hermetter
authors.forename: Günther
authors.initials: G
authors.lastname: Daum
mesh_terms: D000624:5-Aminolevulinate Synthetase / Q000235:genetics / Q000378:metabolism; D002152:Calorimetry, Differential Scanning; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000378:metabolism*; D005454:Fluorescence Polarization; D008401:Gas Chromatography-Mass Spectrometry; D007425:Intracellular Membranes / Q000737:chemistry / Q000378:metabolism; D008055:Lipids / Q000032:analysis* / Q000737:chemistry; D008560:Membrane Fluidity; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D009154:Mutation; D010316:Particle Size; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013185:Squalene / Q000032:analysis* / Q000378:metabolism; D013261:Sterols / Q000737:chemistry / Q000378:metabolism; D013696:Temperature; D013816:Thermodynamics
chemical_list: D008055:Lipids; D008563:Membrane Lipids; D029701:Saccharomyces cerevisiae Proteins; D013261:Sterols; D013185:Squalene; D000624:5-Aminolevulinate Synthetase; C577889:aminolevulinate synthase, S cerevisiae