Mechanisms of Non-Vesicular Exchange of Lipids at Membrane Contact Sites: Of Shuttles, Tunnels and, Funnels.
Mechanisms of Non-Vesicular Exchange of Lipids at Membrane Contact Sites: Of Shuttles, Tunnels and, Funnels.
复制标题
DOI：
10.3389/fcell.2021.784367
复制
发表时间：
2021
影响因子：
5.5
通讯作者：
Egea PF
中科院分区：
文献类型：
--
作者：
Egea PF
真核细胞的特征在于它们由丰富的膜结合细胞器产生的精致的区室化。这些隔室中的每一个都承载一系列生化反应，并支持生物功能，如基因组储存、膜蛋白和脂质生物合成/降解以及ATP合成，这些都是细胞生命所必需的。作为细胞器之间和整个细胞内物质和信号传递的枢纽，膜接触位点（MCS），来自不同细胞器的膜之间的紧密贴壁位点，对细胞内稳态至关重要。现在公认的功能之一的MCS涉及非囊泡贩运的脂质;其表征回答了一个长期存在的问题，揭示了一些细胞器如何接收和分配膜脂的囊泡贩运的情况下，真核细胞生物学。内质网（ER）与线粒体协同作用，通过接触几乎所有其他细胞器类型，成为磷脂（PL）在整个细胞中生物合成和分布的纽带。MCSs产生并维持整个细胞中生物膜的功能不对称性和极性所必需的脂质通量和梯度。膜沉积是由蛋白质系链介导的，其中一些蛋白质系链起脂质转移蛋白（LTP）的作用。我们在这里总结了一些主要类别的LTP和系绳的基础上可用的原子到近原子的分辨率结构的几个“模型”MCSs从酵母，但也在后生动物的机械知识的现状;我们描述了不同的模型的脂质转移在MCSs和分析其特异性和方向性的决定因素。这些系统中的每一个都说明了真核细胞膜结合细胞器之间的脂质非囊泡交换的基本原理和机制，这些细胞器对广泛的细胞过程至关重要，例如PL生物合成和分布，脂质储存，自噬和细胞器生物发生。
Eukaryotic cells are characterized by their exquisite compartmentalization resulting from a cornucopia of membrane-bound organelles. Each of these compartments hosts a flurry of biochemical reactions and supports biological functions such as genome storage, membrane protein and lipid biosynthesis/degradation and ATP synthesis, all essential to cellular life. Acting as hubs for the transfer of matter and signals between organelles and throughout the cell, membrane contacts sites (MCSs), sites of close apposition between membranes from different organelles, are essential to cellular homeostasis. One of the now well-acknowledged function of MCSs involves the non-vesicular trafficking of lipids; its characterization answered one long-standing question of eukaryotic cell biology revealing how some organelles receive and distribute their membrane lipids in absence of vesicular trafficking. The endoplasmic reticulum (ER) in synergy with the mitochondria, stands as the nexus for the biosynthesis and distribution of phospholipids (PLs) throughout the cell by contacting nearly all other organelle types. MCSs create and maintain lipid fluxes and gradients essential to the functional asymmetry and polarity of biological membranes throughout the cell. Membrane apposition is mediated by proteinaceous tethers some of which function as lipid transfer proteins (LTPs). We summarize here the current state of mechanistic knowledge of some of the major classes of LTPs and tethers based on the available atomic to near-atomic resolution structures of several “model” MCSs from yeast but also in Metazoans; we describe different models of lipid transfer at MCSs and analyze the determinants of their specificity and directionality. Each of these systems illustrate fundamental principles and mechanisms for the non-vesicular exchange of lipids between eukaryotic membrane-bound organelles essential to a wide range of cellular processes such as at PL biosynthesis and distribution, lipid storage, autophagy and organelle biogenesis.
登录
查看更多内容
影响因子：
6.8
作者：
Brunner, Janine D.;Schenck, Stephan;Dutzler, Raimund
通讯作者：
Dutzler, Raimund
影响因子：
7.8
作者：
Chang, Chi-Lun;Weigel, Aubrey, V;Lippincott-Schwartz, Jennifer
通讯作者：
Lippincott-Schwartz, Jennifer
影响因子：
16
作者：
Csordás G;Várnai P;Golenár T;Roy S;Purkins G;Schneider TG;Balla T;Hajnóczky G
通讯作者：
Hajnóczky G
影响因子：
64.5
作者：
Bausewein, Thomas;Mills, Deryck J.;Kuehlbrandt, Werner
通讯作者：
Kuehlbrandt, Werner
影响因子：
4
作者：
Balderhaar, Henning J. Kleine;Ungermann, Christian
通讯作者：
Ungermann, Christian