Progress in Lipid Research ( IF 14.0 ) Pub Date : 2022-10-03 , DOI: 10.1016/j.plipres.2022.101195 Colin A Fox 1 , Robert O Ryan 1
Cardiolipin (CL) is a unique phospholipid that is fundamental to the structure and function of the highly curved cristae membranes of mitochondria. Given its distinctive cone-shaped molecular architecture, CL induces negative membrane curvature in a bilayer setting. Another key feature of CL is its intrinsic ability to interact with various ligands, including cytochrome c, the anti-neoplastic anthracycline, doxorubicin, and the divalent cation, calcium. Although these, and other, binding interactions exert profound effects on mitochondrial and cellular function, they are difficult to study in intact mitochondria. Whereas liposomes provide a potential model membrane system, their relatively large size, limited ability to accommodate CL and the presence of an inaccessible interior bilayer leaflet, make these structures suboptimal. The discovery that CL can be formulated into aqueous soluble, reconstituted high density lipoprotein particles, termed nanodisks (ND), provides an alternative model membrane system. Comprised solely of CL and an apolipoprotein scaffold, CL-ND exist as a disk-shaped phospholipid bilayer whose perimeter is stabilized by contact with the scaffold protein. In these nanoscale particles, both leaflets of the bilayer are solvent accessible, an advantage for studies of ligand interactions. Recent experiments employing CL-ND have yielded novel insight into apoptosis, cardiotoxicity and CL-dependent bilayer to non-bilayer transitions.
中文翻译:
心磷脂相互作用组研究
心磷脂 (CL) 是一种独特的磷脂,是线粒体高度弯曲的嵴膜的结构和功能的基础。鉴于其独特的锥形分子结构,CL 在双层环境中诱导负膜曲率。CL 的另一个关键特征是其与各种配体(包括细胞色素c )相互作用的内在能力,抗肿瘤蒽环类药物多柔比星和二价阳离子钙。尽管这些和其他结合相互作用对线粒体和细胞功能产生深远影响,但它们很难在完整的线粒体中进行研究。尽管脂质体提供了一种潜在的模型膜系统,但它们相对较大的尺寸、容纳 CL 的能力有限以及存在难以接近的内部双层小叶,使得这些结构不是最佳的。CL 可以配制成水溶性重构高密度脂蛋白颗粒,称为纳米盘 (ND),这一发现提供了另一种模型膜系统。CL-ND 仅由 CL 和载脂蛋白支架组成,以圆盘状磷脂双层的形式存在,其周边通过与支架蛋白接触而稳定。在这些纳米级颗粒中,双分子层的两个小叶都是溶剂可及的,这是研究配体相互作用的一个优势。最近使用 CL-ND 的实验对细胞凋亡、心脏毒性和依赖 CL 的双层到非双层的转变有了新的认识。