Gatliff Jemma, Campanella Michelangelo
Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street NW1 0TU, London, U.K.
Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street NW1 0TU, London, U.K. University College London Consortium for Mitochondrial Research, Gower Street WC1 6BT, London, United Kingdom
Biochem J. 2016 Jan 15;473(2):107-21. doi: 10.1042/BJ20150899.
The 18-kDa translocator protein (TSPO) localizes in the outer mitochondrial membrane (OMM) of cells and is readily up-regulated under various pathological conditions such as cancer, inflammation, mechanical lesions and neurological diseases. Able to bind with high affinity synthetic and endogenous ligands, its core biochemical function resides in the translocation of cholesterol into the mitochondria influencing the subsequent steps of (neuro-)steroid synthesis and systemic endocrine regulation. Over the years, however, TSPO has also been linked to core cellular processes such as apoptosis and autophagy. It interacts and forms complexes with other mitochondrial proteins such as the voltage-dependent anion channel (VDAC) via which signalling and regulatory transduction of these core cellular events may be influenced. Despite nearly 40 years of study, the precise functional role of TSPO beyond cholesterol trafficking remains elusive even though the recent breakthroughs on its high-resolution crystal structure and contribution to quality-control signalling of mitochondria. All this along with a captivating pharmacological profile provides novel opportunities to investigate and understand the significance of this highly conserved protein as well as contribute the development of specific therapeutics as presented and discussed in the present review.
18 kDa转位蛋白（TSPO）定位于细胞的线粒体外膜（OMM），在各种病理条件下，如癌症、炎症、机械损伤和神经疾病中，它很容易被上调。它能够与合成配体和内源性配体高亲和力结合，其核心生化功能在于将胆固醇转运到线粒体中，影响（神经）甾体合成和全身内分泌调节的后续步骤。然而，多年来，TSPO也与细胞凋亡和自噬等核心细胞过程有关。它与其他线粒体蛋白相互作用并形成复合物，如电压依赖性阴离子通道（VDAC），通过该通道可能影响这些核心细胞事件的信号传导和调节转导。尽管经过了近40年的研究，但TSPO在胆固醇转运之外的确切功能作用仍然难以捉摸，尽管最近在其高分辨率晶体结构以及对线粒体质量控制信号传导的贡献方面取得了突破。所有这些以及引人注目的药理学特性为研究和理解这种高度保守的蛋白质的重要性提供了新的机会，也为如本综述中所介绍和讨论的特定疗法的开发做出了贡献。
