Properties of cardiolipin and functional implications for cytochrome oxidase activity

Cardiolipin derivatives are found to enhance considerably the activity of cytochrome oxidase reconstituted in dimyristoyl phosphatidylcholine, at all substrate concentrations.

Abstract

Cardiolipin derivatives with varying numbers of acyl chains ranging from two to five are found to display a wide variety of polymorphic forms in aqueous dispersion, varying from micelles through bilayers to inverted hexagonal phases. Dilyso cardiolipin and cardiolipin itself are found to change their polymorphic form at high salt concentrations ([NaCl] > 1.5 M), changing from micelle to bilayer or from bilayer to inverted hexagonal phase, respectively. Spin-labelled cardiolipin analogues are found to exhibit a preferential interaction with reconstituted cytochrome oxidase in a dimyristoyl phosphatidylcholine environment. Varying the number of acyl chains in the cardiolipin molecule from three to five is found to have only a small effect on the selectivity of the lipid-protein interaction. Removal of the cardiolipin charge by methylation of the phosphate groups, or screening of the electrostatic interactions by high salt concentrations ([NaCl] > 1.5 M), is found to reduce, but not to abolish, the selectivity. Cardiolipin derivatives are found to enhance considerably the activity of cytochrome oxidase reconstituted in dimyristoyl phosphatidylcholine, at all substrate concentrations. Possible mechanisms for activation by cardiolipin are discussed in the light of the physical measurements.