Steroidogenic activity of StAR requires contact with mitochondrial VDAC1 and phosphate carrier protein.
Steroidogenic activity of StAR requires contact with mitochondrial VDAC1 and phosphate carrier protein.
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DOI：
10.1074/jbc.m709221200
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发表时间：
2008-04-04
期刊：
影响因子：
--
通讯作者：
Bose HS
中科院分区：
文献类型：
--
作者：
Bose M;Whittal RM;Miller WL;Bose HS
类固醇生成急性调节蛋白（星星）是肾上腺和性腺类固醇生成以及男性性别分化所必需的。星星作用于线粒体外膜（OMM），以促进胆固醇从OMM移动到线粒体内膜，转化为所有类固醇激素的前体-双烯醇酮。星星的作用机制尚不清楚;外周苯二氮卓受体（一种OMM蛋白）似乎参与其中，但与星星相互作用的OMM蛋白的身份仍不清楚。在这里，我们表明，磷酸化的星星与电压依赖性阴离子通道1（VDAC 1）的OMM，然后促进37 kDa的磷酸化StAR的32 kDa的中间体的处理相互作用。在缺乏VDAC 1的情况下，磷酸化StAR在线粒体输入之前被半胱氨酸蛋白酶降解。蛋白激酶A对星星的磷酸化需要OMM上的磷酸载体蛋白，该蛋白似乎在与VDAC 1相互作用之前与星星相互作用。VDAC 1和磷酸载体蛋白是显示接触星星的第一个OMM蛋白。
The steroidogenic acute regulatory protein (StAR) is required for adrenal and gonadal steroidogenesis and for male sexual differentiation. StAR acts on the outer mitochondrial membrane (OMM) to facilitate movement of cholesterol from the OMM to the inner mitochondrial membrane to be converted to pregnenolone, the precursor of all steroid hormones. The mechanisms of the action of StAR remain unclear; the peripheral benzodiazepine receptor, an OMM protein, appears to be involved, but the identity of OMM proteins that interact with StAR remain unknown. Here we demonstrate that phosphorylated StAR interacts with voltage-dependent anion channel 1 (VDAC1) on the OMM, which then facilitates processing of the 37-kDa phospho-StAR to the 32-kDa intermediate. In the absence of VDAC1, phospho-StAR is degraded by cysteine proteases prior to mitochondrial import. Phosphorylation of StAR by protein kinase A requires phosphate carrier protein on the OMM, which appears to interact with StAR before it interacts with VDAC1. VDAC1 and phosphate carrier protein are the first OMM proteins shown to contact StAR.