The permeability transition pore as a mitochondrial calcium release channel: A critical appraisal

The permeability transition pore as a mitochondrial calcium release channel: A critical appraisal
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DOI:
10.1007/bf02110643
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发表时间:
1996-04-01
影响因子:
3
通讯作者:
Petronilli, V
Petronilli, V
中科院分区:
生物学4区
文献类型:
--
作者:
Bernardi, P;Petronilli, V

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来自各种来源的线粒体具有内膜通道,即渗透性转换孔。该孔是电压依赖性通道,由基质Ca 2+激活并由基质H+抑制,其可以被环孢菌素A阻断,推测是在与线粒体亲环素结合后。渗透性转换孔的生理功能仍然未知。在这里,我们评估其潜在的作用,作为一个快速的Ca 2+释放通道参与线粒体和细胞的Ca 2+稳态。我们(i)讨论了线粒体需要一个快速的、可诱导的Ca ~(2+)释放通道的理论和实验原因:(ii)分析了线粒体通透性转换孔与肌浆网ryanodine受体-Ca ~(2+)释放通道之间的惊人相似性;(iii)认为渗透性转换孔可以作为Ca 2+的选择性释放通道尽管其明显缺乏选择性的运输物种在体外;和(iv)讨论线粒体在细胞内Ca 2+稳态的重要性,以及如何破坏这一功能可能会影响细胞活力,特别是在氧化应激的条件下。
Mitochondria from a variety of sources possess an inner membrane channel, the permeability transition pore. The pore is a voltage-dependent channel, activated by matrix Ca2+ and inhibited by matrix H+, which can be blocked by cyclosporin A, presumably after binding to mitochondrial cyclophilin. The physiological function of the permeability transition pore remains unknown. Here we evaluate its potential role as a fast Ca2+ release channel involved in mitochondrial and cellular Ca2+ homeostasis. We (i) discuss the theoretical and experimental reasons why mitochondria need a fast, inducible Ca2+ release channel; (ii) analyze the striking analogies between the mitochondrial permeability transition pore and the sarcoplasmic reticulum ryanodine receptor-Ca2+ release channel; (iii) argue that the permeability transition pore can act as a selective release channel for Ca2+ despite its apparent lack of selectivity for the transported species in vitro; and (iv) discuss the importance of mitochondria in cellular Ca2+ homeostasis, and how disruption of this function could impinge upon cell viability, particularly under conditions of oxidative stress.