Effect of Cardiolipin on Proton Permeability of Phospholipid Liposomes: The Role of Hydration at the Lipid–Water Interface

Chen, Qi-Ping; Li, Qiu-Tian

doi:10.1006/abbi.2001.2319

Cited by 19 publications

(10 citation statements)

References 41 publications

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“…It is known that the addition of chol increases hydration at the interfacial head group region of the bilayer [47]; therefore the presence of greater numbers of hydrogen-bonded water molecules in this region might facilitate proton movement into the bilayer at the critical interfacial juncture. Indeed, Chen and Li [48] demonstrated such a phenomenon when they showed that cardiolipin increased the proton permeability of DPPC liposomes by increasing surface hydration. Since head group spacing does not seem to be affected by the incorporation of chol [49], it would seem unlikely that proton permeation is enhanced as a result of charge dilution.…”

Section: Discussionmentioning

confidence: 97%

Lipid raft components cholesterol and sphingomyelin increase H+/OH− permeability of phosphatidylcholine membranes

Gensure

Zeidel

Hill

2006

Biochemical Journal

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H+/OH- permeation through lipid bilayers occurs at anomalously high rates and the determinants of proton flux through membranes are poorly understood. Since all life depends on proton gradients, it is important to develop a greater understanding of proton leak phenomena. We have used stopped-flow fluorimetry to probe the influence of two lipid raft components, chol (cholesterol) and SM (sphingomyelin), on H+/OH- and water permeability. Increasing the concentrations of both lipids in POPC (palmitoyl-2-oleoyl phosphatidylcholine) liposomes decreased water permeability in a concentration-dependent manner, an effect that correlated with increased lipid order. Surprisingly, proton flux was increased by increasing the concentration of chol and SM. The chol effect was complex with molar concentrations of 17.9, 33 and 45.7% giving 2.8-fold (P<0.01), 2.2-fold (P<0.001) and 5.1-fold (P<0.001) increases in H+/OH- permeability from a baseline of 2.4x10(-2) cm/s. SM at 10 mole% effected a 2.8-fold increase (P<0.01), whereas 20 and 30 mole% enhanced permeability by 3.6-fold (P<0.05) and 4.1-fold respectively (P<0.05). Supplementing membranes containing chol with SM did not enhance H+/OH- permeability. Of interest was the finding that chol addition to soya-bean lipids decreased H+/OH- permeability, consistent with an earlier report [Ira and Krishnamoorthy (2001) J. Phys. Chem. B 105, 1484-1488]. We speculate that the presence of proton carriers in crude lipid extracts might contribute to this result. We conclude that (i) chol and SM specifically and independently increase rates of proton permeation in POPC bilayers, (ii) domains enriched in these lipids or domain interfaces may represent regions with high H+/OH- conductivity, (iii) H+/OH- fluxes are not governed by lipid order and (iv) chol can inhibit or promote H+/OH- permeability depending on the total lipid environment. Theories of proton permeation are discussed in the light of these results.

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Section: Discussionmentioning

confidence: 97%

Lipid raft components cholesterol and sphingomyelin increase H+/OH− permeability of phosphatidylcholine membranes

Gensure

Zeidel

Hill

2006

Biochemical Journal

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“…The two major phospholipid species in mitochondrial membranes are phosphatidylcholine (PC) and phosphatidylethanolamine (PE) lipid species. A variety of studies, including monolayer experiments (42)(43)(44)(45), vesicle and bilayer experiments (42,(46)(47)(48), and simulation (49)(50)(51) have probed the biophysical properties of binary mixtures of CL with PC or PE lipids. A limited number of experimental studies have also probed the biophysical properties of more complex lipid mixtures (>ternary) using OMM-like supported lipid bilayers (48) and IMM-like monolayers (45).…”

Section: Introductionmentioning

confidence: 99%

Cardiolipin-Dependent Properties of Model Mitochondrial Membranes from Molecular Dynamics Simulations

Wilson

Ramanathan

López

2019

Preprint

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Cardiolipin is a unique anionic lipid found in mitochondrial membranes where it contributes to various mitochondrial functions, including metabolism, mitochondrial membrane fusion/fission dynamics, and apoptosis. Dysregulation of cardiolipin synthesis and remodeling have also been implicated in several diseases, such as diabetes, heart disease and Barth Syndrome. Although cardiolipin's structural and dynamic roles have been extensively studied in binary mixtures with other phospholipids, the biophysical properties of cardiolipin in ternary lipid mixtures are still not well resolved. Here, we used molecular dynamics simulations to investigate the cardiolipin-dependent properties of ternary lipid bilayer systems that mimic the major components of mitochondrial membranes. We found that changes to cardiolipin concentration only resulted in minor changes to bilayer structural features, but that the lipid diffusion was significantly affected by those alterations. We also found that cardiolipin position along the bilayer surfaces correlated to negative curvature deflections, consistent with the induction of negative curvature stress in the membrane monolayers. This work contributes to a foundational understanding of the role of CL in altering the properties in ternary lipid mixtures composed of the major mitochondrial phospholipids, providing much needed insights to help understand how cardiolipin concentration modulates the biophysical properties of mitochondrial membranes.

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“…Cardiolipin, also referred as to diphosphatidylglycerols, constitutes a class of complex phospholipids that occur mainly in the heart and skeletal muscles and that usually are associated with membranes of subcellular fractions showing high metabolic activity, for example, the mitochondria (1-3). Cardiolipin plays an important role in many biological processes as well as in many areas of biochemical and biomedical studies (4)(5)(6)(7). During the past decade, more attention has been focused on the use of cardiolipin in drug delivery, therapeutic imaging, diagnostic imaging, and as contrast agents (8)(9)(10).…”

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confidence: 99%

An efficient and novel method for the synthesis of cardiolipin and its analogs

Lin¹,

Ahmad²,

Ali³

et al. 2004

Lipids

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A novel synthetic method has been developed for cardiolipin and its analog via a chlorophosphoramidite coupling reaction followed by oxidation. The reagent, N,N-diisopropylmethylphosphoramidic chloride, couples effectively with 1,2-O-dimyristoyl-sn-glycerol in the presence of an amidite activator to form a phosphoamidite intermediate, which then reacts with 2-O-benzylglycerol in the presence of a basic catalyst followed by in situ oxidation to give the corresponding protected cardiolipin. Deprotection of the protecting groups provides tetramyristoyl cardiolipin in good overall yield of 60%. The synthetic method is applicable to large-scale synthesis of cardiolipin and various analogs with or without unsaturation for liposomal drug delivery.

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Effect of Cardiolipin on Proton Permeability of Phospholipid Liposomes: The Role of Hydration at the Lipid–Water Interface

Cited by 19 publications

References 41 publications

Lipid raft components cholesterol and sphingomyelin increase H+/OH− permeability of phosphatidylcholine membranes

Lipid raft components cholesterol and sphingomyelin increase H+/OH− permeability of phosphatidylcholine membranes

Cardiolipin-Dependent Properties of Model Mitochondrial Membranes from Molecular Dynamics Simulations

An efficient and novel method for the synthesis of cardiolipin and its analogs

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