TSPO the unrested: challenged opinions of a resourceful mitochondrial protein
TSPO the unrested: challenged opinions of a resourceful mitochondrial protein
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不安分的 TSPO：对足智多谋的线粒体蛋白的观点提出质疑
DOI：
10.1016/j.tem.2015.05.003
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发表时间：
2015
影响因子：
10.9
通讯作者：
Campanella M
中科院分区：
文献类型：
--
作者：
Campanella M
1202年，数学家斐波那契出版了一本名为《算盘书》的书，描述了一个整数序列，其中每一项都是前两项的和。这种循环关系被证明对解释和编目相互关联的系统很有用，生物学也不例外。尽管与旨在解释周围自然平衡的数学模型的平行可能看起来不合适，TSPO的故事-近40年之久-承载着一系列反复发生的事件，使其成为现代实验生物学的一个活跃领域，包括重新评估，更新，新颖的命名法，当然，激烈的争论。最新的争论认为TSPO作为类固醇生成调节剂的作用[2]，再一次，TSPO的真正功能受到怀疑（或怀疑？），而生物学中的蛋白质被重新命名后，就受到了质疑[2]。有趣的是，这发生在TSPO科学的发展势头中，其特征在于具有根本意义和更广泛相关性的发现，如对其结构的描述[3-5]，以及对通过自噬操作的线粒体的选择性质量控制作用的鉴定[6]。TSPO（Translocator Protein）是外膜（OMM）的一种成分，位于细胞外膜和细胞质之间的界面。作为苯二氮卓类药物的替代结合位点的最初发现-因此外周苯二氮卓受体（PBR）的原始命名-促使目前在实验、临床前和临床水平上使用的许多靶分子的合成。PBR的名称后来被修改为TSPO，以适当地描述线粒体中胆固醇转运蛋白的核心功能，因此是类固醇生成的重要组成部分[7]。重命名也是必要的，以区分PBR/TSPO从中央苯二氮卓类GABA α受体，并区分其替代药理学特征。无论如何，对TSPO的兴趣随着时间的推移而增长，这要归功于其配体在体内成像中的广泛开发和应用，作为评估从创伤到神经变性的炎症性质的脑状况的手段。
In 1202 the mathematician Fibonacci published a book titled the Liber Abaci to describe a sequence of integer numbers in which each of the terms, subsequent to one, is the sum of the preceding two [1]. This recurrent relation proved useful to explain and catalogue interconnecting systems, with no exception of biology. Even though the parallel with a mathematical model that aims to explain the equilibrium of the surrounding nature may look inappropriate, the story–nearly 40 years long–of TSPO, bears an implicit sequence of recurrent events that has made this an active field of modern experimental biology encompassing reassessments, updates, novel nomenclatures and, of course, fierce debates.The latest of these regards its role as steroidogenesis regulator [2], and once again, the true function of TSPO is doubted (or misdoubted?), and the biology after which the protein was renamed is questioned [2]. Interestingly, this takes place in a momentum for TSPO science characterised by discoveries of fundamental significance and broader relevance, as the description of its structure [3–5], and the identification of a role in selective quality control of mitochondria operated by autophagy [6]. TSPO, which stand for Translocator Protein, is a componentoftheoutermitochondrialmembrane (OMM), localised at the interface between mitochondrion and cytosol. The initial discovery as alternative binding site for the benzodiazepines–hence the original nomenclature of Peripheral Benzodiazpeine Receptor (PBR)–has prompted the synthesis of numerous target molecules currently used both at experimental, preclinical and clinical level. The name PBR was later revised to TSPO in order to appropriately describe what emerged to be its core function of cholesterol translocator in the mitochondria, and thus, essential component of steroidogenesis [7]. Renaming was also necessary to distinguish PBR/TSPO from the central benzodiazepine GABAa receptor and to demark its alternative pharmacological profile. The interest on TSPO has anyway grown strong in time, thanking the vast exploitation and applications of its ligands for in vivo imaging, as means to assess brain conditions of inflammatory nature spanning from trauma to neurodegeneration.
DOI：
10.1016/j.tem.2015.04.001
发表时间：
2015-07
期刊：
Trends in endocrinology and metabolism: TEM
影响因子：
--
作者：
Gut P;Zweckstetter M;Banati RB
通讯作者：
Banati RB
DOI：
10.1126/science.1248725
发表时间：
2014-03-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Jaremko L;Jaremko M;Giller K;Becker S;Zweckstetter M
通讯作者：
Zweckstetter M