Institute of Theoretical and Experimental Biophysics, RAS, Pushchino, 142290 Moscow, Russia.
Department of Molecular Pathobiology, College of Dentistry, New York University, New York, NY 10010, USA.
Cells. 2021 Jan 11;10(1):125. doi: 10.3390/cells10010125.
A sharp increase in the permeability of the mitochondrial inner membrane known as mitochondrial permeability transition (or mPT) occurs in mitochondria under the conditions of Ca and ROS stress. Permeability transition can proceed through several mechanisms. The most common mechanism of mPT is based on the opening of a cyclosporine A (CSA)-sensitive protein channel in the inner membrane. In addition to the CSA-sensitive pathway, mPT can occur through the transient opening of lipid pores, emerging in the process of formation of palmitate/Ca complexes. This pathway is independent of CSA and likely plays a protective role against Ca and ROS toxicity. The review considers molecular mechanisms of formation and regulation of the palmitate/Ca-induced pores, which we designate as PA-mPT to distinguish it from the classical CSA-sensitive mPT. In the paper, we discuss conditions of its opening in the biological membranes, as well as its role in the physiological and pathophysiological processes. Additionally, we summarize data that indicate the involvement of PA-mPT in the protection of mitochondria against calcium overload and glutamate-induced degradation in neurons.
线粒体通透性转变（mitochondrial permeability transition，mPT）是指线粒体内膜通透性的急剧增加，这种情况通常发生在 Ca 和 ROS 应激条件下的线粒体中。通透性转变可以通过几种机制发生。mPT 最常见的机制是基于内膜中环孢素 A（cyclosporine A，CSA）敏感蛋白通道的打开。除了 CSA 敏感途径外，mPT 还可以通过脂质孔的短暂打开发生，这种脂质孔在形成棕榈酸/Ca 复合物的过程中出现。该途径不依赖于 CSA，可能在对抗 Ca 和 ROS 毒性方面发挥保护作用。本综述考虑了形成和调节棕榈酸/Ca 诱导的孔的分子机制，我们将其命名为 PA-mPT，以将其与经典的 CSA 敏感 mPT 区分开来。本文讨论了其在生物膜中打开的条件，以及其在生理和病理生理过程中的作用。此外，我们总结了表明 PA-mPT 参与保护线粒体免受钙超载和谷氨酸诱导的神经元降解的相关数据。
