Mitochondrial cholesterol import
Mitochondrial cholesterol import
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DOI：
10.1016/j.bbalip.2016.08.012
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发表时间：
2017-01-01
影响因子：
4.8
通讯作者：
Karten, Barbara
中科院分区：
文献类型：
--
作者：
Elustondo, Pia;Martin, Laura A.;Karten, Barbara
所有动物的亚细胞膜都需要胆固醇，胆固醇影响膜的流动性和渗透性、分裂和融合过程以及膜蛋白的功能。胆固醇在亚细胞膜中的分布是高度不均匀的，必须仔细调节每个膜的胆固醇含量。与其他亚细胞膜相比，线粒体膜是胆固醇贫乏的，特别是线粒体内膜（IMM）。因此，类固醇生成可以通过将胆固醇递送到IMM来控制，在IMM中胆固醇转化为双烯醇酮。低基础胆固醇水平也使线粒体对胆固醇含量的变化敏感，这可能对线粒体膜的生物物理和功能特征产生相对较大的影响。线粒体胆固醇水平增加已在多种病理条件下观察到，包括癌症、脂肪性肝炎、阿尔茨海默病和尼曼-匹克型Cl-缺乏症，并且与氧化应激增加、氧化磷酸化受损和细胞凋亡易感性变化以及线粒体中的其他改变相关！功能线粒体不包括在囊泡运输网络中;因此，胆固醇转运到线粒体主要是通过膜接触位点处的脂质转移蛋白的活性或通过胞质、可扩散的脂质转移蛋白实现的。在这里，我们将概述线粒体胆固醇输入的主要机制，重点是类固醇生成急性调节蛋白星星/STARDI和其他成员的StAR相关的脂质转移（START）结构域蛋白家族，我们将讨论如何在线粒体胆固醇水平的变化可以出现和影响线粒体功能。本文是由Guenther Daum编辑的题为：线粒体脂质的特刊的一部分。(C)2016爱思唯尔B. V.保留所有权利。
All animal subcellular membranes require cholesterol, which influences membrane fluidity and permeability, fission and fusion processes, and membrane protein function. The distribution of cholesterol among subcellular membranes is highly heterogeneous and the cholesterol content of each membrane must be carefully regulated. Compared to other subcellular membranes, mitochondrial membranes are cholesterol-poor, particularly the inner mitochondrial membrane (IMM). As a result, steroidogenesis can be controlled through the delivery of cholesterol to the IMM, where it is converted to pregnenolone. The low basal levels of cholesterol also make mitochondria sensitive to changes in cholesterol content, which can have a relatively large impact on the biophysical and functional characteristics of mitochondrial membranes. Increased mitochondrial cholesterol levels have been observed in diverse pathological conditions including cancer, steatohepatitis, Alzheimer disease and Niemann-Pick Type Cl-deficiency, and are associated with increased oxidative stress, impaired oxidative phosphorylation, and changes in the susceptibility to apoptosis, among other alterations in mitochondria! function. Mitochondria are not included in the vesicular trafficking network; therefore, cholesterol transport to mitochondria is mostly achieved through the activity of lipid transfer proteins at membrane contact sites or by cytosolic, diffusible lipid transfer proteins. Here we will give an overview of the main mechanisms involved in mitochondrial cholesterol import, focusing on the steroidogenic acute regulatory protein StAR/STARDI and other members of the StAR-related lipid transfer (START) domain protein family, and we will discuss how changes in mitochondrial cholesterol levels can arise and affect mitochondrial function. This article is part of a Special Issue entitled: Lipids of Mitochondria edited by Guenther Daum. (C) 2016 Elsevier B.V. All rights reserved.