Role of mitochondria in steroidogenesis
Role of mitochondria in steroidogenesis
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DOI：
10.1016/j.beem.2012.05.002
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发表时间：
2012-12-01
影响因子：
7.4
通讯作者：
Miller, Walter L.
中科院分区：
文献类型：
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作者：
Papadopoulos, Vassilios;Miller, Walter L.
肾上腺、性腺、胎盘和脑线粒体含有几种类固醇生成酶，特别是胆固醇侧链裂解酶P450scc，它是类固醇生成的酶限速步骤，决定了细胞的类固醇生成能力。甚至在这一步之前，胆固醇对这一酶系统的访问既是限速的，也是通过类固醇生成的急性调节蛋白(STAR)与外部线粒体上复杂的多组分“转导小体”相互作用的。膜(OMM)。转导小体的组成包括18 kDa转位蛋白(TSPO)、电压依赖性阴离子通道(VDAC-1)、TSPO相关蛋白7(PAP7，酰基辅酶A结合区3的ACBD3)和蛋白激酶A调节亚基1α(PKAR1A)。这些蛋白质相互作用并将胆固醇从OMM转移到P450scc的确切方式，以及胆固醇被加载到OMM的方式仍不清楚。STAR和P450scc已经描述了人类的缺乏症。线粒体还含有几种“下游”类固醇生成酶。(C)2012爱思唯尔有限公司。保留所有权利。
Adrenal gonadal, placental and brain mitochondria contain several steroidogenic enzymes, notably the cholesterol side chain cleavage enzyme, P450scc, which is the enzymatic rate-limiting step in steroidogenesis which determines cellular steroidogenic capacity. Even before this step, the access of cholesterol to this enzyme system is both rate-limiting and the site of acute regulation via the steroidogenic acute regulatory protein (StAR) which interacts with a complex multi-component 'transduceosome' on the outer mitochondria! membrane (OMM). The components of the transduceosome include the 18 kDa translocator protein (TSPO), the voltage-dependent anion channel (VDAC-1), TSPO-associated protein 7 (PAP7, ACBD3 for acyl-CoA-binding-domain 3), and protein kinase A regulatory subunit 1 alpha (PKAR1A). The precise fashion in which these,proteins interact and move cholesterol from the OMM to P450scc, and the means by which cholesterol is loaded into the OMM, remain unclear. Human deficiency diseases have been described for StAR and for P450scc. Mitochondria also contain several 'downstream' steroidogenic enzymes. (C) 2012 Elsevier Ltd. All rights reserved.