Human Health, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.
Discipline of Medical Imaging & Radiation Sciences, Faculty of Medicine and Health, Brain and Mind Centre, University of Sydney, 94 Mallett Street, Camperdown, NSW 2050, Australia.
Cells. 2020 Feb 24;9(2):512. doi: 10.3390/cells9020512.
The translocator protein (TSPO) is an outer mitochondrial membrane protein that is widely used as a biomarker of neuroinflammation, being markedly upregulated in activated microglia in a range of brain pathologies. Despite its extensive use as a target in molecular imaging studies, the exact cellular functions of this protein remain in question. The long-held view that TSPO plays a fundamental role in the translocation of cholesterol through the mitochondrial membranes, and thus, steroidogenesis, has been disputed by several groups with the advent of TSPO knockout mouse models. Instead, much evidence is emerging that TSPO plays a fundamental role in cellular bioenergetics and associated mitochondrial functions, also part of a greater role in the innate immune processes of microglia. In this review, we examine the more direct experimental literature surrounding the immunomodulatory effects of TSPO. We also review studies which highlight a more central role for TSPO in mitochondrial processes, from energy metabolism, to the propagation of inflammatory responses through reactive oxygen species (ROS) modulation. In this way, we highlight a paradigm shift in approaches to TSPO functioning.
转位蛋白（TSPO）是一种位于线粒体外膜的蛋白，作为神经炎症的生物标志物被广泛应用，在多种脑疾病中，TSPO 在激活的小胶质细胞中显著上调。尽管它被广泛用作分子成像研究的靶点，但该蛋白的确切细胞功能仍存在争议。随着 TSPO 敲除小鼠模型的出现，长期以来认为 TSPO 在胆固醇通过线粒体膜的易位以及类固醇生成中发挥基本作用的观点受到了几个研究小组的质疑。相反，越来越多的证据表明 TSPO 在细胞生物能量学和相关的线粒体功能中发挥着基本作用，这也是 TSPO 在小胶质细胞固有免疫过程中发挥更大作用的一部分。在这篇综述中，我们研究了围绕 TSPO 免疫调节作用的更直接的实验文献。我们还回顾了一些研究，这些研究强调了 TSPO 在线粒体功能中的更核心作用，从能量代谢到通过调节活性氧物质（ROS）来传播炎症反应。通过这种方式，我们强调了 TSPO 功能研究方法的范式转变。
