Ionization constants pKa of cardiolipin

PLoS One. 2013 Sep 13;8(9):e73040. doi: 10.1371/journal.pone.0073040. eCollection 2013.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteria / chemistry
  • Cardiolipins / chemistry*
  • Dimerization
  • Humans
  • Hydrogen-Ion Concentration
  • Mitochondrial Membranes / chemistry
  • Solutions
  • Titrimetry


  • Cardiolipins
  • Solutions

Grant support

The Swedish Research Council (VR) is gratefully acknowledged for financial support both through regular grants and the Linnaeus Center of Excellence “Organizing molecular matter” (ES). ES acknowledges The Swedish Foundation for Strategic Research (SSF) for financial support. Knut and Alice Wallenberg's foundation funded the acquisition of the ITC equipment. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.