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线粒体融合与类固醇生成急性调节蛋白(StAR)磷酸化在StAR活性调节及类固醇生成中的作用

The role of mitochondrial fusion and StAR phosphorylation in the regulation of StAR activity and steroidogenesis.

作者信息

Castillo Ana F, Orlando Ulises, Helfenberger Katia E, Poderoso Cecilia, Podesta Ernesto J

机构信息

Biomedical Research Institute, INBIOMED, Department of Biochemistry, School of Medicine University of Buenos Aires, Ciudad Autónoma de Buenos Aires (CABA), C1121ABG, Argentina.

Biomedical Research Institute, INBIOMED, Department of Biochemistry, School of Medicine University of Buenos Aires, Ciudad Autónoma de Buenos Aires (CABA), C1121ABG, Argentina.

出版信息

Mol Cell Endocrinol. 2015 Jun 15;408:73-9. doi: 10.1016/j.mce.2014.12.011. Epub 2014 Dec 22.

Abstract

The steroidogenic acute regulatory (StAR) protein regulates the rate-limiting step in steroidogenesis, i.e. the delivery of cholesterol from the outer (OMM) to the inner (IMM) mitochondrial membrane. StAR is a 37-kDa protein with an N-terminal mitochondrial targeting sequence that is cleaved off during mitochondrial import to yield 30-kDa intramitochondrial StAR. StAR acts exclusively on the OMM and its activity is proportional to how long it remains on the OMM. However, the precise fashion and the molecular mechanism in which StAR remains on the OMM have not been elucidated yet. In this work we will discuss the role of mitochondrial fusion and StAR phosphorylation by the extracellular signal-regulated kinases 1/2 (ERK1/2) as part of the mechanism that regulates StAR retention on the OMM and activity.

摘要

类固醇生成急性调节(StAR)蛋白调节类固醇生成中的限速步骤,即胆固醇从线粒体外膜(OMM)转运至线粒体内膜(IMM)。StAR是一种37 kDa的蛋白质,其N端有线粒体靶向序列,在导入线粒体过程中该序列被切除,产生30 kDa的线粒体内StAR。StAR仅作用于线粒体外膜,其活性与它在线粒体外膜上停留的时间成正比。然而,StAR在线粒体外膜上停留的精确方式和分子机制尚未阐明。在这项工作中,我们将讨论线粒体融合以及细胞外信号调节激酶1/2(ERK1/2)介导的StAR磷酸化的作用,这是调节StAR在线粒体外膜上的滞留及其活性机制的一部分。

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