Cardiolipins have multiple vital functions within biological cell membranes, most notably in the energy metabolism associated with the inner mitochondrial membrane. Considering their essential role, peroxidation of cardiolipins may plausibly have significant effects, as peroxidation is known to alter the functionality of lipid molecules. We used atomistic molecular dynamics simulations to study how peroxidation of cardiolipin affects the properties of the inner mitochondrial membrane. To this end, we explored what happens when varying fractions of fatty acid chains of cardiolipin are replaced by its four different oxidized products in systems modeling the inner mitochondrial membrane. We found that the oxidation of cardiolipin leads to a conformational change both in the backbone/head group and in chain regions of oxidized cardiolipin molecules. The oxidized groups were observed to shift closer to the membrane-water interface region, where they formed hydrogen bonds with several other groups. Additionally, the conformational change turned out to decrease bilayer thickness, and to increase the area per lipid chain, though these changes were minor. The acyl chain conformational order of unoxidized lipids exposed to interactions with oxidized cardiolipins was increased in carbons 3–5 and decreased in carbons 13–17 due to the structural reorganization of the cardiolipin molecules. Overall, the results bring up that the conformation of cardiolipin is altered upon oxidation, suggesting that its oxidation may interfere its interactions with mitochondrial proteins and thereby affect cardiolipin-dependent cellular processes such as electron and proton transport.

心磷脂在生物细胞膜内具有多种重要功能，最明显的是在与线粒体内膜有关的能量代谢中。考虑到它们的基本作用，心磷脂的过氧化可能具有明显的作用，因为已知过氧化会改变脂质分子的功能。我们使用原子分子动力学模拟来研究心磷脂的过氧化如何影响线粒体内膜的特性。为此，我们探索了在模拟内部线粒体膜的系统中，当心磷脂的不同脂肪酸链部分被其四种不同的氧化产物所取代时会发生什么。我们发现，心磷脂的氧化导致主链/头部基团和氧化的心磷脂分子的链区中的构象变化。观察到氧化基团向膜-水界面区域移近，在那里它们与其他几个基团形成氢键。另外，构象变化证明减小了双层厚度，并增加了每个脂质链的面积，尽管这些变化很小。由于心磷脂分子的结构重组，暴露于与氧化心磷脂相互作用的未氧化脂质的酰基链构象顺序在碳3–5中增加，在碳13–17中降低。总的来说，结果表明，心磷脂的构象在氧化时会改变，表明其氧化可能会干扰其与线粒体蛋白的相互作用，从而影响心磷脂依赖的细胞过程，例如电子和质子转运。