The combination of calcium overload and oxidative stress opens a non-specific pore in the inner mitochondrial membrane known as the mitochondrial permeability transition pore (MPTP). This uncouples oxidative phosphorylation and compromises intracellular ATP levels eventually leading to necrotic cell death. In cardiac ischemia and reperfusion, as during treatment of a coronary thrombosis or cardiac surgery, the extent of MPTP opening determines the amount of irreversible damage (infarct size). Furthermore, cardioprotection can be achieved by inhibiting MPTP opening either directly with cyclosporin A analogues, or indirectly by reducing oxidative stress. The detailed molecular mechanism of the MPTP remains uncertain. Knockout studies have confirmed important regulatory roles for cyclophilin-D (CyP-D) and the adenine nucleotide translocase (ANT) but not the voltage dependent anion channel. Our own studies have implicated a calcium-triggered conformational change of the mitochondrial phosphate carrier that is facilitated by CyP-D and modulated by the conformation of the ANT.

中文翻译：

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心脏的线粒体和再灌注损伤——一个空洞的死亡，但并非无法拯救。

钙过载和氧化应激的结合在线粒体内膜中打开了一个非特异性孔，称为线粒体通透性转换孔 (MPTP)。这会解耦氧化磷酸化并损害细胞内 ATP 水平，最终导致细胞坏死。在心脏缺血和再灌注中，如在治疗冠状动脉血栓形成或心脏手术期间，MPTP 开放的程度决定了不可逆损伤的量（梗塞面积）。此外，可以通过直接用环孢菌素 A 类似物或通过减少氧化应激间接抑制 MPTP 的开放来实现心脏保护。MPTP 的详细分子机制仍不确定。敲除研究证实了亲环蛋白-D (CyP-D) 和腺嘌呤核苷酸转位酶 (ANT) 的重要调节作用，但不是电压依赖性阴离子通道。我们自己的研究表明，由 CyP-D 促进并受 ANT 构象调节的线粒体磷酸盐载体的钙触发构象变化。