Cardiolipin Structure and Oxidation Are Affected by Ca 2+ at the Interface of Lipid Bilayers

• Published in: Frontiers in chemistry 2019, Vol.7, p.930
• Main Authors: Miranda, Érica G A, Araujo-Chaves, Juliana C, Kawai, Cintia, Brito, Adrianne M M, Dias, Igor W R, Arantes, Jeverson T, Nantes-Cardoso, Iseli L
• Format: Article
• Language: English
• ISSN: 2296-2646; 2296-2646

Ca -overload contributes to the oxidation of mitochondrial membrane lipids and associated events such as the permeability transition pore (MPTP) opening. Numerous experimental studies about the Ca /cardiolipin (CL) interaction are reported in the literature, but there are few studies in conjunction with theoretical approaches based on calculations. In the present study, the lipid fraction of the inner mitochondrial membrane was modeled as POPC/CL large unilamellar vesicles (LUVs). POPC/CL and, comparatively, POPC, and CL LUVs were challenged by singlet molecular oxygen using the anionic porphyrin TPPS4 as a photosensitizer and by free radicals produced by Fe -citrate. Calcium ion favored both types of lipid oxidation in a lipid composition-dependent manner. In membranes containing predominantly or exclusively POPC, Ca increased the oxidation at later reaction times while the oxidation of CL membranes was exacerbated at the early times of reaction. Considering that Ca interaction affects the lipid structure and packing, density functional theory (DFT) calculations were applied to the Ca association with totally and partially protonated and deprotonated CL, in the presence of water. The interaction of totally and partially protonated CL head groups with Ca decreased the intramolecular P-P distance and increased the hydrophobic volume of the acyl chains. Consistently with the theoretically predicted effect of Ca on CL, in the absence of pro-oxidants, giant unilamellar vesicles (GUVs) challenged by Ca formed buds and many internal vesicles. Therefore, Ca induces changes in CL packing and increases the susceptibility of CL to the oxidation promoted by free radicals and excited species.