Department of Biomedical Sciences and CNR Institute of Neuroscience, University of Padova, Italy.
FEBS Lett. 2010 May 17;584(10):1989-96. doi: 10.1016/j.febslet.2010.02.022. Epub 2010 Feb 11.
The permeability transition pore (PTP) is an inner mitochondrial membrane channel that has been thoroughly characterized functionally, yet remains an elusive molecular entity. The best characterized PTP-regulatory component, cyclophilin (CyP) D, is a matrix protein that favors pore opening. CyP inhibitors, CyP-D null animals, and in situ PTP readouts have established the role of PTP as an effector mechanism of cell death, and the growing definition of PTP signalling mechanisms. This review briefly covers the functional features of the PTP and the role played by its dysregulation in disease pathogenesis. Recent progress on PTP modulation by kinase/phosphatase signal transduction is discussed, with specific emphasis on hexokinase and on the Akt-ERK-GSK3 axis, which might modulate the PTP through CyP-D phosphorylation.
通透性转换孔（PTP）是一种线粒体内膜通道，其功能已得到深入研究，但仍然是一个难以捉摸的分子实体。最具特征性的 PTP 调节成分，亲环素（CyP）D，是一种有利于孔道开放的基质蛋白。CyP 抑制剂、CyP-D 缺失动物和原位 PTP 读数已经确立了 PTP 作为细胞死亡效应机制的作用，以及 PTP 信号转导机制的不断发展。本综述简要介绍了 PTP 的功能特征及其在疾病发病机制中的失调作用。讨论了激酶/磷酸酶信号转导对 PTP 调节的最新进展，特别强调了己糖激酶和 Akt-ERK-GSK3 轴，它们可能通过 CyP-D 磷酸化来调节 PTP。
