Evolutionary origin of the mitochondrial cholesterol transport machinery reveals a universal mechanism of steroid hormone biosynthesis in animals.
Evolutionary origin of the mitochondrial cholesterol transport machinery reveals a universal mechanism of steroid hormone biosynthesis in animals.
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DOI：
10.1371/journal.pone.0076701
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Papadopoulos V
中科院分区：
文献类型：
--
作者：
Fan J;Papadopoulos V
类固醇生成开始于胆固醇从细胞内储存通过一系列蛋白质-蛋白质相互作用转运到线粒体中，所述蛋白质-蛋白质相互作用涉及位于线粒体外膜和线粒体内膜的胞质和线粒体蛋白。在肾上腺和性腺中，激素加速了这一过程，导致产生高水平的类固醇，控制组织发育和功能。最近发现了一种胆固醇诱导的多蛋白复合物，即转导体，它由细胞溶质和线粒体外膜蛋白组成，这些蛋白控制胆固醇进入线粒体外膜的速率。最近的研究揭示了类固醇生成代谢子，一种生物活性的多聚体蛋白复合物，跨越外-内线粒体膜，负责线粒体内膜中细胞色素P450家族11亚家族A多肽1（CYP 11 A1）诱导的胆固醇输入、分离、靶向和代谢。基因组信息的可用性使我们能够系统地探索参与线粒体胆固醇转运机制的蛋白质（transtranstranseosome，类固醇代谢子和信号蛋白）的进化起源，追踪原始原型，并通过分子系统发育和功能差异分析，蛋白质同源性建模和分子对接来预测它们的生物学功能。虽然这些复合体的大多数成员在进化过程中有基因复制和功能分歧的历史，但基因组分析显示，所有脊椎动物都有相同的功能复合体成员，这表明类固醇合成的第一步有一个共同的机制。在无脊椎动物中发现了这种复合体的原型。本文提供的数据表明，胆固醇转运机制是负责类固醇在所有脊椎动物和整个动物界的进化保守。
Steroidogenesis begins with the transport of cholesterol from intracellular stores into mitochondria via a series of protein-protein interactions involving cytosolic and mitochondrial proteins located at both the outer and inner mitochondrial membranes. In adrenal glands and gonads, this process is accelerated by hormones, leading to the production of high levels of steroids that control tissue development and function. A hormone-induced multiprotein complex, the transduceosome, was recently identified, and is composed of cytosolic and outer mitochondrial membrane proteins that control the rate of cholesterol entry into the outer mitochondrial membrane. More recent studies unveiled the steroidogenic metabolon, a bioactive, multimeric protein complex that spans the outer-inner mitochondrial membranes and is responsible for hormone-induced import, segregation, targeting, and metabolism of cholesterol by cytochrome P450 family 11 subfamily A polypeptide 1 (CYP11A1) in the inner mitochondrial membrane. The availability of genome information allowed us to systematically explore the evolutionary origin of the proteins involved in the mitochondrial cholesterol transport machinery (transduceosome, steroidogenic metabolon, and signaling proteins), trace the original archetype, and predict their biological functions by molecular phylogenetic and functional divergence analyses, protein homology modeling and molecular docking. Although most members of these complexes have a history of gene duplication and functional divergence during evolution, phylogenomic analysis revealed that all vertebrates have the same functional complex members, suggesting a common mechanism in the first step of steroidogenesis. An archetype of the complex was found in invertebrates. The data presented herein suggest that the cholesterol transport machinery is responsible for steroidogenesis among all vertebrates and is evolutionarily conserved throughout the entire animal kingdom.
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影响因子：
4.1
作者：
Burton, M;Rose, TM;Knudsen, J
通讯作者：
Knudsen, J
DOI：
10.1074/jbc.m709221200
发表时间：
2008-04-04
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Bose M;Whittal RM;Miller WL;Bose HS
通讯作者：
Bose HS
影响因子：
5.3
作者：
Gilquin, Benoit;Taillebourg, Emmanuel;Baudier, Jacques
通讯作者：
Baudier, Jacques
DOI：
10.1016/j.jsbmb.2006.01.003
发表时间：
2006-06-01
影响因子：
4.1
作者：
Cano, Florencia;Poderoso, Cecilia;Podesta, Ernesto J.
通讯作者：
Podesta, Ernesto J.
影响因子：
14.9
作者：
Berka K;Hanák O;Sehnal D;Banás P;Navrátilová V;Jaiswal D;Ionescu CM;Svobodová Vareková R;Koca J;Otyepka M
通讯作者：
Otyepka M