Abstract

Cardiolipin (CL) plays a central role in lipid peroxidation (LPO) of the mitochondrial inner membrane due to higher content of unsaturated fatty acids in CL in comparison with the other phospholipids. CL oxidation plays an important role in the regulation of various intracellular signaling pathways and its excessive oxidation contributes to the development of various pathologies and, possibly, participates in the aging process. Mitochondria-targeted antioxidants containing triphenylphosphonium (TPP⁺) effectively protect CL from oxidation. It is assumed that fluorescent probes on the basis of the C11-BODIPY fluorophore sensitive to LPO and containing TPP⁺ can selectively register CL oxidation. To test this possibility, we carried out a molecular dynamic simulation of such probes in a model mitochondrial membrane. It is shown that the probes are located in the membrane at the same depth as the unsaturated bonds in CL molecules sensitive to oxidation. Increasing the length of the linker that binds the fluorophore and TPP⁺ residue ha little effect on the position of the probe in the membrane. This indicates the possibility of modifying the linker to increase the selectivity of the probes to CL.

中文翻译：

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阳离子荧光脂质过氧化敏感探针与线粒体膜相互作用的分子动力学模型。

摘要

由于与其他磷脂相比，CL中不饱和脂肪酸的含量较高，心磷脂（CL）在线粒体内膜的脂质过氧化（LPO）中起着核心作用。CL氧化在各种细胞内信号传导途径的调节中起着重要作用，其过度的氧化作用促进了各种病理的发展，并可能参与了衰老过程。含有三苯基phosph（TPP ⁺）的线粒体靶向抗氧化剂可有效保护CL免受氧化。假定基于对LPO敏感并含有TPP ⁺的C11-BODIPY荧光团的荧光探针可以选择性地记录CL氧化。为了测试这种可能性，我们在模型线粒体膜中进行了此类探针的分子动力学模拟。结果表明，探针位于膜中的深度与对氧化敏感的CL分子中的不饱和键相同。增加与荧光团和TPP ⁺残基结合的接头的长度，对探针在膜中的位置几乎没有影响。这表明修饰接头以增加探针对CL的选择性的可能性。