Midzak Andrew, Zirkin Barry, Papadopoulos Vassilios
The Research Institute of the McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada Department of Medicine, McGill University, Montreal, Quebec H4A 3J1, Canada
Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, U.S.A.
Biochem Soc Trans. 2015 Aug;43(4):572-8. doi: 10.1042/BST20150061. Epub 2015 Aug 3.
The translocator protein (TSPO; 18k Da) is an evolutionarily conserved outer mitochondrial membrane (OMM) protein highly expressed in steroid-synthesizing cells and found to possess a number of physiological and drug-binding partners. Extensive pharmacological, biochemical and cell biological research over the years has led to a model of TSPO involvement in mitochondrial cholesterol transport and promotion of steroid synthesis, a model guiding the design of drugs useful in stimulating neurosteroid synthesis and alleviating psychopathological symptoms. The involvement of TSPO in these processes has been called into question; however, with the publication of TSPO-deletion mouse models which saw no changes in steroid production. Here, we review work characterizing TSPO in steroidogenesis and offer perspective to research into TSPO pharmacology and its involvement in steroid biosynthesis.
转位蛋白(TSPO;18kDa)是一种在进化上保守的线粒体外膜(OMM)蛋白,在类固醇合成细胞中高度表达,并且已发现它有许多生理和药物结合伴侣。多年来广泛的药理学、生物化学和细胞生物学研究已形成了一个TSPO参与线粒体胆固醇转运和促进类固醇合成的模型,该模型指导了用于刺激神经类固醇合成和减轻精神病理症状的药物设计。然而,TSPO在这些过程中的参与受到了质疑;不过,随着TSPO基因敲除小鼠模型的发表,发现类固醇生成没有变化。在这里,我们综述了在类固醇生成中表征TSPO的工作,并为TSPO药理学及其参与类固醇生物合成的研究提供观点。