Impact of Antioxidants on Cardiolipin Oxidation in Liposomes: Why Mitochondrial Cardiolipin Serves as an Apoptotic Signal?

Figure 1

Schematic representation of the initial steps of CL peroxidation as based on [4, 10, 15–17]. The mammalian heart CL is mostly found in the form of tetralinoleoyl-CL, that is, with four polyunsaturated residues of linoleic acid (I). A bis-allylic hydrogen atom of CL may be abstracted by a peroxyl radical (ROO^∙) yielding peroxide (ROOH) and a lipid-centered radical (II). The latter is involved in a fast reaction with molecular oxygen and turns into another peroxyl radical, which may consequently attack another polyunsaturated lipid in a chain process. This reaction is accompanied by rearrangement of double bonds of the fatty acid residue, which ultimately leads to the accumulation of conjugated dienes (III). Peroxide of CL exposes its nascent hydrophilic moiety at the surface of the membrane, where it may interact with cytochrome and turn it into a peroxidase, thus forcing amplification of the oxidation cascade (IV).