SNAREs and cholesterol movement for steroidogenesis.
SNAREs and cholesterol movement for steroidogenesis.
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DOI：
10.1016/j.mce.2016.07.034
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发表时间：
2017-02-05
影响因子：
4.1
通讯作者：
Azhar S
中科院分区：
文献类型：
--
作者：
Kraemer FB;Shen WJ;Azhar S
类固醇生成是一个复杂的过程，通过该过程胆固醇运输到线粒体，并通过一系列酶促步骤转化为类固醇激素。虽然这一过程中的限速步骤是胆固醇通过星星的作用从线粒体外膜向线粒体内膜移动，但在活跃的类固醇生成过程中，必须向线粒体外膜持续供应胆固醇，这来自多种来源，包括脂蛋白摄取、内源性胆固醇合成和细胞质脂滴内储存的胆固醇释放。已经提出了许多机制来促进胆固醇运输到线粒体;然而，没有明确的共识，尤其是关于从细胞质脂滴的运输。在本文中，我们审查的实验中，我们已经调查了SNARE蛋白在类固醇生成的组织和细胞的表达，并研究了SNARE介导的胆固醇运动的作用，从脂滴的线粒体的基础上，确定SNARE作为细胞质脂滴的组成部分的多项研究。我们建立并表征了体外线粒体重建测定系统，该系统使我们能够检查添加重组SNARE蛋白特异性地对胆固醇从模型脂滴到线粒体外膜的运动的影响。使用这种重组分析系统结合siRNA敲低实验在大鼠原代颗粒细胞或类固醇生成细胞系中，我们发现，几个陷阱蛋白的胆固醇从脂滴到线粒体的类固醇生成的运输中的重要组成部分。
Steroidogenesis is a complex process through which cholesterol traffics to mitochondria and is converted via a series of enzymatic steps to steroid hormones. Although the rate-limiting step in this process is the movement of cholesterol from the outer to the inner mitochondrial membrane via the actions of StAR, a continuous supply of cholesterol must be delivered to the outer mitochondrial membrane during active steroidogenesis and this is derived from multiple sources, including lipoprotein uptake, endogenous cholesterol synthesis and release from stores within cytoplasmic lipid droplets. A number of mechanisms have been suggested to contribute to cholesterol trafficking to mitochondria; however, there is no definitive consensus and this is particularly so in regards to trafficking from cytoplasmic lipid droplets. In this paper we review experiments in which we have surveyed the expression of SNARE proteins in steroidogenic tissue and cells and examined the role of SNAREs in mediating cholesterol movement from lipid droplets to the mitochondria based on multiple studies that identified SNAREs as components of cytoplasmic lipid droplets. We established and characterized an in vitro mitochondria reconstitution assay system that enabled us to examine the impact of adding recombinant SNARE proteins specifically on the movement of cholesterol from model lipid droplets to the outer mitochondrial membrane. Using this reconstitution assay system in combination with siRNA knockdown experiments in rat primary granulosa cells or in steroidogenic cell lines, we showed that several SNARE proteins are important components in the trafficking of cholesterol from lipid droplets to the mitochondria for steroidogenesis.