In this review, we summarize current knowledge of perhaps one of the most intriguing phenomena in cell biology: the mitochondrial permeability transition pore (mPTP). This phenomenon, which was initially observed as a sudden loss of inner mitochondrial membrane impermeability caused by excessive calcium, has been studied for almost 50 years, and still no definitive answer has been provided regarding its mechanisms. From its initial consideration as an in vitro artifact to the current notion that the mPTP is a phenomenon with physiological and pathological implications, a long road has been travelled. We here summarize the role of mitochondria in cytosolic calcium control and the evolving concepts regarding the mitochondrial permeability transition (mPT) and the mPTP. We show how the evolving mPTP models and mechanisms, which involve many proposed mitochondrial protein components, have arisen from methodological advances and more complex biological models. We describe how scientific progress and methodological advances have allowed milestone discoveries on mPTP regulation and composition and its recognition as a valid target for drug development and a critical component of mitochondrial biology.

中文翻译：

---

线粒体通透性转换孔：一个对细胞生死至关重要的不断发展的概念

在这篇综述中，我们总结了当前关于细胞生物学中最有趣的现象之一的知识：线粒体通透性转换孔 (mPTP)。这种现象最初被观察为由过量钙引起的线粒体内膜不透性突然丧失，已经研究了近 50 年，但仍然没有就其机制提供明确的答案。从最初考虑作为体外对于目前认为 mPTP 是一种具有生理和病理意义的现象的观念，人工制品已经走过了漫长的道路。我们在这里总结了线粒体在细胞溶质钙控制中的作用以及关于线粒体通透性转变 (mPT) 和 mPTP 的不断发展的概念。我们展示了不断发展的 mPTP 模型和机制，包括许多提出的线粒体蛋白成分，是如何从方法学进步和更复杂的生物模型中产生的。我们描述了科学进步和方法学进步如何使 mPTP 调控和组成方面的里程碑式发现成为可能，并将其作为药物开发的有效目标和线粒体生物学的关键组成部分。