研究动态
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研究心磷脂相互作用组学。

Studies of the cardiolipin interactome.

发表日期:2022 Nov
作者: Colin A Fox, Robert O Ryan
来源: PROGRESS IN LIPID RESEARCH

摘要:

心磷脂(CL)是一种独特的磷脂,对线粒体高度弯曲的克里斯蒂膜的结构和功能至关重要。由于其具有锥形分子结构,CL在双层设置下引起负曲率膜。CL的另一个关键特征是其与各种配体的内在结合能力,包括细胞色素c、抗肿瘤蒽环素多柔比星和双价阳离子钙等。虽然这些和其他结合作用对线粒体和细胞功能产生深远影响,但它们在完整的线粒体中难以研究。而脂质体提供了一个潜在的模型膜系统,但它们的相对较大尺寸、有限的适应CL的能力以及存在不可接近的内部双层膜叶使得这些结构不太理想。发现CL可以制成水溶性可重构高密度脂蛋白粒子,称为纳米盘(ND),提供了一种替代的模型膜系统。CL-ND仅由CL和一个载脂蛋白支架构成,存在为圆盘形的磷脂双层,其周长通过与支架蛋白的接触稳定。在这些纳米尺度的粒子中,双层的两层膜叶都可以被溶剂访问,这对于研究配体相互作用是一个优势。最近使用CL-ND进行的实验已经为凋亡、心脏毒性和CL依赖的双层到非双层转换提供了新的见解。© 2022 Elsevier Ltd.版权所有。
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.Copyright © 2022 Elsevier Ltd. All rights reserved.