Starke Ilka, Glick Gary D, Börsch Michael
Single-Molecule Microscopy Group, Jena University Hospital, Friedrich Schiller University, Jena, Germany.
Institute for Physical Chemistry, Albert Ludwigs University of Freiburg, Freiburg, Germany.
Front Physiol. 2018 Jul 4;9:803. doi: 10.3389/fphys.2018.00803. eCollection 2018.
Targeting the mitochondrial enzyme FF-ATP synthase and modulating its catalytic activities with small molecules is a promising new approach for treatment of autoimmune diseases. The immunomodulatory compound Bz-423 is such a drug that binds to subunit OSCP of the mitochondrial FF-ATP synthase and induces apoptosis increased reactive oxygen production in coupled, actively respiring mitochondria. Here, we review the experimental progress to reveal the binding of Bz-423 to the mitochondrial target and discuss how subunit rotation of FF-ATP synthase is affected by Bz-423. Briefly, we report how Förster resonance energy transfer can be employed to colocalize the enzyme and the fluorescently tagged Bz-423 within the mitochondria of living cells with nanometer resolution.
靶向线粒体酶FF-ATP合酶并用小分子调节其催化活性是治疗自身免疫性疾病的一种有前景的新方法。免疫调节化合物Bz-423就是这样一种药物，它与线粒体FF-ATP合酶的OSCP亚基结合，并在偶联的、活跃呼吸的线粒体中诱导细胞凋亡、增加活性氧的产生。在此，我们回顾了揭示Bz-423与线粒体靶点结合的实验进展，并讨论了FF-ATP合酶的亚基旋转是如何受到Bz-423影响的。简要地说，我们报告了如何利用Förster共振能量转移以纳米分辨率在活细胞的线粒体内将该酶与荧光标记的Bz-423共定位。
