Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy.
Molecules. 2021 Oct 26;26(21):6463. doi: 10.3390/molecules26216463.
The permeability transition (PT) is an increased permeation of the inner mitochondrial membrane due to the opening of the PT pore (PTP), a Ca-activated high conductance channel involved in Ca homeostasis and cell death. Alterations of the PTP have been associated with many pathological conditions and its targeting represents an incessant challenge in the field. Although the modulation of the PTP has been extensively explored, the lack of a clear picture of its molecular nature increases the degree of complexity for any target-based approach. Recent advances suggest the existence of at least two mitochondrial permeability pathways mediated by the F-ATP synthase and the ANT, although the exact molecular mechanism leading to channel formation remains elusive for both. A full comprehension of this to-pore conversion will help to assist in drug design and to develop pharmacological treatments for a fine-tuned PT regulation. Here, we will focus on regulatory mechanisms that impinge on the PTP and discuss the relevant literature of PTP targeting compounds with particular attention to F-ATP synthase and ANT.
通透性转换（PT）是由于线粒体内膜通透性增加而导致的，这是由于 PT 孔（PTP）的开放，PTP 是一种钙激活的高电导通道，参与钙稳态和细胞死亡。PTP 的改变与许多病理状况有关，其靶向治疗是该领域的一个持续挑战。尽管已经广泛探索了 PTP 的调节，但由于对其分子性质缺乏清晰的认识，任何基于靶标的方法的复杂性都增加了。最近的进展表明，至少有两种由 F-ATP 合酶和 ANT 介导的线粒体通透性途径的存在，尽管对于这两种途径，导致通道形成的确切分子机制仍不清楚。对这种孔转换的全面理解将有助于辅助药物设计，并开发针对精细调节 PT 的药理学治疗方法。在这里，我们将重点讨论影响 PTP 的调节机制，并讨论与 PTP 靶向化合物相关的文献，特别关注 F-ATP 合酶和 ANT。
