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The ionization properties of cardiolipin and its variants in model bilayers
- Source :
- Biochimica et Biophysica Acta (BBA) - Biomembranes. 1858(6):1362-1372
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- The anionic phospholipid cardiolipin has an unusual dimeric structure with a two-phosphate headgroup and four acyl chains. Cardiolipin is present in energy-transducing membranes that maintain electrochemical gradients, including most bacterial plasma membranes and the mitochondrial inner membrane, where it mediates respiratory complex assembly and activation, among many other roles. Dysfunctional biogenesis of cardiolipin is implicated in the pathogenesis of several diseases including Barth syndrome. Because cardiolipin is a dominant anionic lipid in energy-conserving membranes, its headgroup is a major contributor to surface charge density and the bilayer electrostatic profile. However, the proton dissociation behavior of its headgroup remains controversial. In one model, the pKa values of the phosphates differ by several units and the headgroup exists as a monoanion at physiological pH. In another model, both phosphates ionize as strong acids with low pKa values and the headgroup exists in dianionic form at physiological pH. Using independent electrokinetic and spectroscopic approaches, coupled with analysis using Gouy–Chapman–Stern formalism, we have analyzed the ionization properties of cardiolipin within biologically relevant lipid bilayer model systems. We show that both phosphates of the cardiolipin headgroup show strong ionization behavior with low pKa values. Moreover, cardiolipin variants lacking structural features proposed to be required to maintain disparate pKa values – namely the secondary hydroxyl on the central glycerol or a full complement of four acyl chains – were shown to have ionization behavior identical to intact cardiolipin. Hence, these results indicate that within the physiological pH range, the cardiolipin headgroup is fully ionized as a dianion. We discuss the implications of these results with respect to the role of cardiolipin in defining membrane surface potential, activating respiratory complexes, and modulating membrane curvature.
- Subjects :
- 0301 basic medicine
Cardiolipins
Lipid Bilayers
Static Electricity
Phospholipid
Biophysics
Biochemistry
Article
03 medical and health sciences
chemistry.chemical_compound
Cardiolipin
Inner mitochondrial membrane
Lipid bilayer
Ions
030102 biochemistry & molecular biology
Bilayer
Cell Biology
Hydrogen-Ion Concentration
030104 developmental biology
Membrane
Models, Chemical
chemistry
Membrane curvature
lipids (amino acids, peptides, and proteins)
Subjects
Details
- ISSN :
- 00052736
- Volume :
- 1858
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Biochimica et Biophysica Acta (BBA) - Biomembranes
- Accession number :
- edsair.doi.dedup.....fb77a07c32b4a0dcf1e21d9601ac7c73
- Full Text :
- https://doi.org/10.1016/j.bbamem.2016.03.007