Department of Molecular Pharmacology, Technion-Israel Institute of Technology, P.O. Box 9649, Bat-Galim, Haifa 31096, Israel.
Curr Mol Med. 2012 May;12(4):398-412. doi: 10.2174/1566524011207040398.
The mitochondrial 18 kDa Translocator Protein (TSPO) was first detected by its capability to bind benzodiazepines in peripheral tissues and later also in glial cells in the brain, hence its previous most common name peripheral benzodiazepine receptor (PBR). TSPO has been implicated in various functions, including apoptosis and steroidogenesis, among others. Various endogenous TSPO ligands have been proposed, for example: Diazepam Binding Inhibitor (DBI), triakontatetraneuropeptide (TTN), phospholipase A2 (PLA2), and protoporphyrin IX. However, the functional implications of interactions between the TSPO and its putative endogenous ligands still have to be firmly established. The TSPO has been suggested to interact with a mitochondrial protein complex, summarized as mitochondrial membrane permeability transition pore (MPTP), which is considered to regulate the mitochondrial membrane potential (ΔΨm). In addition, the TSPO is associated with several other proteins. The associations of the TSPO with these various proteins at the mitochondrial membranes have been attributed to functions such as apoptosis, steroidogenesis, phosphorylation, reactive oxygen species (ROS) generation, ATP production, and collapse of the ΔΨm. Interestingly, while TSPO is known to play a role in the modulation of steroid production, in turn, steroids are also known to affect TSPO expression. As with the putative endogenous TSPO ligands, the effects of steroids on TSPO functions still have to be established. In any case, steroid-TSPO interactions occur in organs and tissues as diverse as the reproductive system, kidney, and brain. In general, the steroid-TSPO interactions are thought to be part of stress responses, but may also be essential for reproductive events, embryonic development, and responses to injury, including brain injury. The present review focuses on the role of TSPO in cell death i.e. the notion that enhanced expression and/or activation of the TSPO leads to cell death, and the potential of steroids to regulate TSPO expression and activation.
线粒体 18kDa 转位蛋白（TSPO）最初因其在周围组织中结合苯二氮䓬类药物的能力而被检测到，后来也在大脑中的神经胶质细胞中被检测到，因此它之前最常见的名称是外周苯二氮䓬受体（PBR）。TSPO 被认为参与了各种功能，包括细胞凋亡和类固醇生成等。已经提出了各种内源性 TSPO 配体，例如：地西泮结合抑制剂（DBI）、三烷十肽（TTN）、磷脂酶 A2（PLA2）和原卟啉 IX。然而，TSPO 与其假定的内源性配体之间相互作用的功能意义仍有待确定。TSPO 被认为与一个线粒体蛋白复合物相互作用，概括为线粒体膜通透性转换孔（MPTP），它被认为可以调节线粒体膜电位（ΔΨm）。此外，TSPO 还与其他几种蛋白质相关。TSPO 与线粒体膜上的这些各种蛋白质的关联归因于细胞凋亡、类固醇生成、磷酸化、活性氧（ROS）生成、ATP 产生和ΔΨm 的崩溃等功能。有趣的是，虽然 TSPO 已知在调节类固醇生成中起作用，但反过来，类固醇也已知会影响 TSPO 的表达。与假定的内源性 TSPO 配体一样，类固醇对 TSPO 功能的影响仍有待确定。无论如何，类固醇-TSPO 相互作用发生在生殖系统、肾脏和大脑等各种器官和组织中。一般来说，类固醇-TSPO 相互作用被认为是应激反应的一部分，但对于生殖事件、胚胎发育和对损伤的反应（包括脑损伤）也可能是必不可少的。本综述重点介绍 TSPO 在细胞死亡中的作用，即增强 TSPO 的表达和/或激活会导致细胞死亡，以及类固醇调节 TSPO 表达和激活的潜力。
