Adult cardiomyocytes are postmitotic cells that undergo very limited cell division. Thus, cardiomyocyte death as occurs during myocardial infarction has very detrimental consequences for the heart. Mitochondria have emerged as an important regulator of cardiovascular health and disease. Mitochondria are well established as bioenergetic hubs for generating ATP but have also been shown to regulate cell death pathways. Indeed many of the same signals used to regulate metabolism and ATP production, such as calcium and reactive oxygen species, are also key regulators of mitochondrial cell death pathways. It is widely hypothesized that an increase in calcium and reactive oxygen species activate a large conductance channel in the inner mitochondrial membrane known as the PTP (permeability transition pore) and that opening of this pore leads to necroptosis, a regulated form of necrotic cell death. Strategies to reduce PTP opening either by inhibition of PTP or inhibiting the rise in mitochondrial calcium or reactive oxygen species that activate PTP have been proposed. A major limitation of inhibiting the PTP is the lack of knowledge about the identity of the protein(s) that form the PTP and how they are activated by calcium and reactive oxygen species. This review will critically evaluate the candidates for the pore-forming unit of the PTP and discuss recent data suggesting that assumption that the PTP is formed by a single molecular identity may need to be reconsidered.

中文翻译：

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线粒体钙和通透性过渡孔在调节细胞死亡中的作用。

成体心肌细胞是细胞分裂非常有限的有丝分裂后细胞。因此，在心肌梗塞期间发生的心肌细胞死亡对心脏具有非常有害的后果。线粒体已成为心血管健康和疾病的重要调节剂。线粒体作为产生 ATP 的生物能量中心已被很好地确立，但也已被证明可以调节细胞死亡途径。事实上，许多用于调节代谢和 ATP 产生的相同信号，例如钙和活性氧，也是线粒体细胞死亡途径的关键调节剂。人们普遍假设，钙和活性氧的增加会激活线粒体内膜中的一个大电导通道，称为 PTP（通透性转换孔），并且该孔的打开会导致坏死性凋亡，这是一种受调控的坏死细胞死亡形式。已经提出了通过抑制 PTP 或抑制激活 PTP 的线粒体钙或活性氧的升高来减少 PTP 开放的策略。抑制 PTP 的一个主要限制是缺乏关于形成 PTP 的蛋白质的身份以及它们如何被钙和活性氧物质激活的知识。