Molecular Inflammation Group, Biomedical Research Institute of Murcia, Clinical University Hospital Virgen de la Arrixaca (IMIB-Arrixaca), Carretera Buenavista s/n, Murcia 30120, Spain.
Molecular Inflammation Group, Biomedical Research Institute of Murcia, Clinical University Hospital Virgen de la Arrixaca (IMIB-Arrixaca), Carretera Buenavista s/n, Murcia 30120, Spain.
Trends Cell Biol. 2020 Nov;30(11):892-903. doi: 10.1016/j.tcb.2020.09.004. Epub 2020 Sep 30.
Cardiolipin (CL) is a tetra-acylated diphosphatidylglycerol lipid. In physiological conditions, CL presents unsaturated chains and is located in the inner mitochondria membrane (IMM). Dead signals, infection, or disease may change the level of CL saturation and oxidation and cause its translocation to the cytosolic side of the outer mitochondrial membrane (OMM), affecting mitochondrial function and the inflammatory response. In this review, we summarize the emerging proapoptotic, pro-, and anti-inflammatory functions of cytosolic-exposed CL and how they are regulated by CL chain saturation and oxidation. We underline how the unique dimeric phospholipid structure confers peculiar properties on CL in the regulation of cell death and immune system proteins, such as the Nucleotide-binding domain and leucine-rich repeat-containing pyrin protein 3 (NLRP3), caspases (Casp), and Toll-like receptor 4 (TLR4). We also provide an overview of the human diseases in which CL deficiency or modification are implicated and of the use of exogenous unsaturated CL (uCL) as a novel therapeutic approach.
心磷脂（CL）是一种四酰化二磷酸甘油脂质。在生理条件下，CL 呈现不饱和链，位于线粒体内膜（IMM）中。死亡信号、感染或疾病可能会改变 CL 饱和度和氧化水平，并导致其易位到线粒体外膜（OMM）的胞质侧，影响线粒体功能和炎症反应。在这篇综述中，我们总结了胞质暴露的 CL 新出现的促凋亡、促炎和抗炎功能，以及 CL 链饱和度和氧化如何调节这些功能。我们强调了独特的二聚磷脂结构如何在心磷脂对细胞死亡和免疫系统蛋白（如核苷酸结合域和富含亮氨酸重复的含吡咯蛋白 3（NLRP3）、半胱天冬酶（Casp）和 Toll 样受体 4（TLR4））的调节中赋予其特殊性质。我们还概述了 CL 缺乏或修饰所涉及的人类疾病，以及外源性不饱和 CL（uCL）作为一种新的治疗方法的应用。
