Mitochondrial calcium and the permeability transition in cell death.

Mitochondrial calcium and the permeability transition in cell death.
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DOI:
10.1016/j.bbabio.2009.06.009
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发表时间:
2009-11
影响因子:
4.3
通讯作者:
Nieminen, Anna-Liisa
Nieminen, Anna-Liisa
中科院分区:
生物学2区
文献类型:
--
作者:
Lemasters, John J.;Theruvath, Tom P.;Zhong, Zhi;Nieminen, Anna-Liisa

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长期以来,Ca 2+的调节异常在细胞损伤中起重要作用。在坏死和凋亡(或坏死三聚体)中重要的Ca 2+连接的过程是线粒体通透性转换(MPT)。在MPT中,大的电导渗透性转换(PT)孔打开,使线粒体内膜突然渗透溶质高达1500 Da.Ca2+在MPT诱导的重要性随环境而变化。Ca 2+超载足以诱导MPT。相反,心肌细胞缺血-再灌注后,Ca 2+超载是MPT后生物能量衰竭的结果,而不是其原因。在其他模型中,如Reye相关药物的细胞毒性和肝移植物的储存-再灌注损伤,Ca 2+似乎允许MPT的发生。最后,在氧化应激中,增加的线粒体Ca 2+和ROS产生协同作用,产生MPT和细胞死亡。因此,Ca 2+诱导MPT和细胞死亡的确切作用取决于特定的生物学环境。
Dysregulation of Ca2+ has long been implicated to be important in cell injury. A Ca2+-linked process important in necrosis and apoptosis (or necrapoptosis) is the mitochondrial permeability transition (MPT). In the MPT, large conductance permeability transition (PT) pores open that make the mitochondrial inner membrane abruptly permeable to solutes up to 1500 Da. The importance of Ca2+ in MPT induction varies with circumstance. Ca2+ overload is sufficient to induce the MPT. By contrast after ischemia-reperfusion to cardiac myocytes, Ca2+ overload is the consequence of bioenergetic failure after the MPT rather than its cause. In other models, such as cytotoxicity from Reye-related agents and storage-reperfusion injury to liver grafts, Ca2+ appears to be permissive to MPT onset. Lastly in oxidative stress, increased mitochondrial Ca2+ and ROS generation act synergistically to product the MPT and cell death. Thus, the exact role of Ca2+ for inducing the MPT and cell death depends on the particular biologic setting.
DOI: 10.1042/bss0660167
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