Lemasters John J, Theruvath Tom P, Zhong Zhi, Nieminen Anna-Liisa
Center for Cell Death, Injury and Regeneration, Medical University of South Carolina, Charleston, SC 29425, USA.
Biochim Biophys Acta. 2009 Nov;1787(11):1395-401. doi: 10.1016/j.bbabio.2009.06.009. Epub 2009 Jul 1.
Dysregulation of Ca(2+) has long been implicated to be important in cell injury. A Ca(2+)-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 Ca(2+) in MPT induction varies with circumstance. Ca(2+) overload is sufficient to induce the MPT. By contrast after ischemia-reperfusion to cardiac myocytes, Ca(2+) 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, Ca(2+) appears to be permissive to MPT onset. Lastly in oxidative stress, increased mitochondrial Ca(2+) and ROS generation act synergistically to produce the MPT and cell death. Thus, the exact role of Ca(2+) for inducing the MPT and cell death depends on the particular biologic setting.
长期以来，钙离子（Ca(2+)）调节异常被认为在细胞损伤中起重要作用。线粒体通透性转换（MPT）是一个与坏死和凋亡（或坏死性凋亡）相关的重要Ca(2+)连接过程。在MPT中，大电导通透性转换（PT）孔开放，使线粒体内膜突然对分子量高达1500 Da的溶质具有通透性。Ca(2+)在MPT诱导中的重要性因情况而异。Ca(2+)过载足以诱导MPT。相比之下，心肌细胞缺血再灌注后，Ca(2+)过载是MPT后生物能衰竭的结果而非原因。在其他模型中，如与瑞氏综合征相关药物的细胞毒性和肝移植的储存再灌注损伤，Ca(2+)似乎允许MPT发生。最后，在氧化应激中，线粒体Ca(2+)增加和活性氧生成协同作用，导致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。
