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首页> 美国卫生研究院文献>The Journal of Biological Chemistry >Regulation of the Mitochondrial Permeability Transition Pore by the Outer Membrane Does Not Involve the Peripheral Benzodiazepine Receptor (Translocator Protein of 18 kDa (TSPO))
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Regulation of the Mitochondrial Permeability Transition Pore by the Outer Membrane Does Not Involve the Peripheral Benzodiazepine Receptor (Translocator Protein of 18 kDa (TSPO))

机译：外膜对线粒体通透性转变孔的调节不涉及周围的苯二氮卓类受体（18 kDa转运蛋白（TSPO））

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Translocator protein of 18 kDa (TSPO) is a highly conserved, ubiquitous protein localized in the outer mitochondrial membrane, where it is thought to play a key role in the mitochondrial transport of cholesterol, a key step in the generation of steroid hormones. However, it was first characterized as the peripheral benzodiazepine receptor because it appears to be responsible for high affinity binding of a number of benzodiazepines to non-neuronal tissues. Ensuing studies have employed natural and synthetic ligands to assess the role of TSPO function in a number of natural and pathological circumstances. Largely through the use of these compounds and biochemical associations, TSPO has been proposed to play a role in the mitochondrial permeability transition pore (PTP), which has been associated with cell death in many human pathological conditions. Here, we critically assess the role of TSPO in the function of the PTP through the generation of mice in which the Tspo gene has been conditionally eliminated. Our results show that 1) TSPO plays no role in the regulation or structure of the PTP, 2) endogenous and synthetic ligands of TSPO do not regulate PTP activity through TSPO, 3) outer mitochondrial membrane regulation of PTP activity occurs though a mechanism that does not require TSPO, and 4) hearts lacking TSPO are as sensitive to ischemia-reperfusion injury as hearts from control mice. These results call into question a wide variety of studies implicating TSPO in a number of pathological processes through its actions on the PTP.
机译：18 kDa转运蛋白（TSPO）是高度保守的遍在蛋白，位于线粒体外膜，据认为在胆固醇的线粒体运输中起关键作用，胆固醇是类固醇激素产生的关键步骤。然而，它首先被表征为外周苯并二氮杂receptor受体，因为它似乎负责许多苯并二氮杂to与非神经元组织的高亲和力结合。随后的研究已经采用天然和合成的配体来评估TSPO功能在许多自然和病理情况下的作用。主要是通过使用这些化合物和生物化学联系，TSPO被认为在线粒体通透性过渡孔（PTP）中起作用，该孔与许多人类病理状况下的细胞死亡有关。在这里，我们通过产生Tspo基因已被有条件消除的小鼠，来严格评估TSPO在PTP功能中的作用。我们的结果表明，1）TSPO在PTP的调节或结构中不起作用，2）TSPO的内源和合成配体不通过TSPO调节PTP活性，3）线粒体外膜调节PTP活性的机理是不需要TSPO，并且4）缺乏TSPO的心脏对缺血-再灌注损伤的敏感性与对照小鼠的心脏一样。这些结果使人们对各种各样的研究产生疑问，这些研究通过其对PTP的作用将TSPO牵涉到许多病理过程中。

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