Effect of cholesterol on the structure of a five-component mitochondria-like phospholipid membrane

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DOIResolve DOI: http://doi.org/10.3390/membranes5040664
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TypeArticle
Journal titleMembranes
ISSN2077-0375
Volume5
Issue4
Pages664684
Subjectphospholipid; cholesterol; mitochondria; cardiolipin; apoptosis; Bax; X-ray diffraction; reflectivity; wide angle X-ray scattering
AbstractCellular membranes have a complex phospholipid composition that varies greatly depending on the organism, cell type and function. In spite of this complexity, most structural data available for phospholipid bilayers concern model systems containing only one or two different phospholipids. Here, we examine the effect of cholesterol on the structure of a complex membrane reflecting the lipid composition of mitochondrial membranes, with five different types of headgroups (phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS) and cardiolipin (CL)) and a variety of hydrocarbon tails. This particular system was chosen because elevated cholesterol contents in mitochondrial membranes have been linked to a breaking down of Bax-mediated membrane permeabilization and resistance to cancer treatments. High resolution electron density profiles were determined by X-ray reflectivity, while the area per phospholipid chain, Apc, and the chain order parameter, SX-ray, were determined by wide-angle X-ray scattering (WAXS). We show that chain order increases upon the addition of cholesterol, resulting in both a thickening of the lipid bilayer and a reduction in the average surface area per phospholipid chain. This effect, well known as cholesterol’s condensation effect, is similar, but not as pronounced as for single-component phospholipid membranes. We conclude by discussing the relevance of these findings for the insertion of the pro-apoptotic protein Bax in mitochondrial membranes with elevated cholesterol content.
Publication date
LanguageEnglish
AffiliationSecurity and Disruptive Technologies; National Research Council Canada
Peer reviewedYes
NPARC number23000978
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Record identifier3bba7355-39ea-41a9-b7b3-365c4d09d15e
Record created2016-11-23
Record modified2016-11-23
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