Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra 50, 40064, Ozzano Emilia, BO, Italy.
Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra 50, 40064, Ozzano Emilia, BO, Italy.
Biochimie. 2018 Sep;152:85-93. doi: 10.1016/j.biochi.2018.06.022. Epub 2018 Jun 28.
Based on recent advances on the Ca-activated FF-ATPase features, a novel multistep mechanism involving the mitochondrial FF complex in the formation and opening of the still enigmatic mitochondrial permeability transition pore (MPTP), is proposed. MPTP opening makes the inner mitochondrial membrane (IMM) permeable to ions and solutes and, through cascade events, addresses cell fate to death. Since MPTP forms when matrix Ca concentration rises and ATP is hydrolyzed by the FF-ATPase, conformational changes, triggered by Ca insertion in F, may be transmitted to F and locally modify the IMM curvature. These events would cause FF-ATPase dimer dissociation and MPTP opening.
基于最近在 Ca 激活的 FF-ATP 酶特性方面的进展，提出了一种新的多步骤机制，涉及线粒体 FF 复合物在形成和打开仍然神秘的线粒体通透性转换孔 (MPTP) 中的作用。MPTP 的打开使线粒体内膜 (IMM) 对离子和溶质具有通透性，并通过级联事件决定细胞的命运走向死亡。由于 MPTP 形成时基质 Ca 浓度升高，并且 FF-ATP 酶水解 ATP，因此 F 中 Ca 插入引发的构象变化可能传递到 F 并局部改变 IMM 曲率。这些事件将导致 FF-ATP 酶二聚体解离和 MPTP 打开。
