Interaction between cardiolipin and the mitochondrial presequence of cytochrome c oxidase subunit IV favours lipid mixing without destabilizing the bilayer structure.

We demonstrate the ability of a peptide corresponding to the presequence of the cytochrome c oxidase subunit IV to induce lipid mixing between large unilamellar liposomes. This lipid mixing requires the presence of CL or PE, lipids able to form non-bilayer structures, and is not observed with other negatively charged lipids. However, the fact that this mixing occurs without mixing of the liposome aqueous phases and without destabilizing the lipid organisation is unusual and has not been observed for other amphiphilic peptides. This observation supports the idea that the presequence could play a role in the formation of translocation contact sites between the two mitochondrial membranes and facilitate the structural rearrangements of the outer and inner membrane proteins involved in the two import machineries in a way to permit the formation of a continuous import channel through the two mitochondrial membranes without mixing the cytoplasmic and mitochondrial aqueous contents.