School of Life Science, Shandong University of Technology, Zibo, Shandong Province, China.
Department of Pharmacy, Shenzhen Luohu People's Hospital, Shenzhen, Guangdong Province, China.
Mol Cell Biochem. 2021 Jan;476(1):493-506. doi: 10.1007/s11010-020-03926-0. Epub 2020 Sep 30.
Mitochondria have various cellular functions, including ATP synthesis, calcium homeostasis, cell senescence, and death. Mitochondrial dysfunction has been identified in a variety of disorders correlated with human health. Among the many underlying mechanisms of mitochondrial dysfunction, the opening up of the mitochondrial permeability transition pore (mPTP) is one that has drawn increasing interest in recent years. It plays an important role in apoptosis and necrosis; however, the molecular structure and function of the mPTP have still not been fully elucidated. In recent years, the abnormal opening up of the mPTP has been implicated in the development and pathogenesis of diverse diseases including ischemia/reperfusion injury (IRI), neurodegenerative disorders, tumors, and chronic obstructive pulmonary disease (COPD). This review provides a systematic introduction to the possible molecular makeup of the mPTP and summarizes the mitochondrial dysfunction-correlated diseases and highlights possible underlying mechanisms. Since the mPTP is an important target in mitochondrial dysfunction, this review also summarizes potential treatments, which may be used to inhibit pore opening up via the molecules composing mPTP complexes, thus suppressing the progression of mitochondrial dysfunction-related diseases.
线粒体具有多种细胞功能，包括 ATP 合成、钙稳态、细胞衰老和死亡。线粒体功能障碍已在与人类健康相关的多种疾病中得到证实。在导致线粒体功能障碍的众多潜在机制中，线粒体通透性转换孔（mPTP）的开放近年来引起了越来越多的关注。它在细胞凋亡和坏死中发挥重要作用；然而，mPTP 的分子结构和功能尚未完全阐明。近年来，mPTP 的异常开放与多种疾病的发生和发病机制有关，包括缺血/再灌注损伤（IRI）、神经退行性疾病、肿瘤和慢性阻塞性肺疾病（COPD）。本综述系统介绍了 mPTP 的可能分子组成，并总结了与线粒体功能障碍相关的疾病，并强调了可能的潜在机制。由于 mPTP 是线粒体功能障碍的重要靶点，本综述还总结了潜在的治疗方法，这些方法可能通过组成 mPTP 复合物的分子来抑制孔的开放，从而抑制与线粒体功能障碍相关的疾病的进展。
