Department of Biomedical Sciences, University of Padova and CNR Neuroscience Institute, Via Ugo Bassi 58/B, I-35131 Padova, Italy.
Department of Biomedical Sciences, University of Padova and CNR Neuroscience Institute, Via Ugo Bassi 58/B, I-35131 Padova, Italy.
Cell Calcium. 2023 May;111:102719. doi: 10.1016/j.ceca.2023.102719. Epub 2023 Mar 21.
The mitochondrial Permeability Transition Pore (PTP) can be defined as a Ca activated mega-channel involved in mitochondrial damage and cell death, making its inhibition a hallmark for therapeutic purposes in many PTP-related paradigms. Although long-lasting PTP openings have been widely studied, the physiological implications of transient openings (also called "flickering" behavior) are still poorly understood. The flickering activity was suggested to play a role in the regulation of Ca and ROS homeostasis, and yet this hypothesis did not reach general consensus. This state of affairs might arise from the lack of unquestionable experimental evidence, due to limitations of the available techniques for capturing transient PTP activity and to a still partial understanding of its molecular identity. In this review we will focus on possible implications of the PTP in physiology, in particular its role as a Ca release pathway, discussing the consequences of its forced inhibition. We will also consider the recent hypothesis of the existence of more permeability pathways and their potential involvement in mitochondrial physiology.
线粒体通透性转换孔（PTP）可被定义为一种钙激活的巨型通道，参与线粒体损伤和细胞死亡，因此其抑制作用成为许多与 PTP 相关范式中治疗目的的标志。尽管人们对长时间开放的 PTP 进行了广泛的研究，但对短暂开放（也称为“闪烁”行为）的生理意义仍知之甚少。闪烁活动被认为在调节 Ca 和 ROS 动态平衡中发挥作用，但这一假说尚未得到普遍共识。这种情况可能是由于缺乏无可置疑的实验证据，这是由于现有技术捕捉短暂 PTP 活性的局限性以及对其分子身份的部分理解所致。在这篇综述中，我们将重点讨论 PTP 在生理学中的可能意义，特别是它作为 Ca 释放途径的作用，讨论其强制抑制的后果。我们还将考虑最近关于存在更多通透性途径的假说及其在线粒体生理学中的潜在作用。
