Abstract

Cardiolipin is a phospholipid found in the inner mitochondrial membrane and in bacteria, and it is associated with many physiological functions. Cardiolipin has a dimeric structure consisting of two phosphatidyl residues connected by a glycerol bridge and four acyl chains, and therefore it can carry two negative charges. The pKa values of the phosphate groups have previously been reported to differ widely with pKa1 = 2.8 and pKa2 = 7.5–9.5. Still, there are several examples of experimental observations from cardiolipin-containing systems that do not fit with this dissociation behavior. Therefore, we have carried out pH-titration and titration calorimetric experiments on two synthetic cardiolipins, 1,1′,2,2′-tetradecanoyl cardiolipin, CL (C14∶0), and 1,1′,2,2′-tetraoctadecenoyl cardiolipin, CL (C18∶1). Our results show that both behave as strong dibasic acids with pKa1 about the same as the first pKa of phosphoric acid, 2.15, and pKa2 about one unit larger. The characterization of the acidic properties of cardiolipin is crucial for the understanding of the molecular organization in self-assembled systems that contain cardiolipin, and for their biological function.

Highlights

  • Cardiolipin is a phospholipid found in the inner mitochondrial membrane and in most bacteria

  • It has a dimeric structure consisting two phosphatidyl residues connected by a glycerol bridge and four acyl chains, and it can carry two negative charges

  • This agrees with the observation by Seddon et al, who reported a transition from lamellar phase to inverse hexagonal phase in cardiolipin-water systems upon lowering pH to below 2.8, which is consistent with a reduction of the effective head group area due to reduced electrostatic repulsion [14]

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Summary

Introduction

Cardiolipin is a phospholipid found in the inner mitochondrial membrane and in most bacteria. In a later study by Kates et al, the pKa values of cardiolipin were reported to differ widely with a low pKa of 2.8 and a second varying from 7.5 to 9.5 [19,20].

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