Mitochondrial membrane permeability transition and cell death
Mitochondrial membrane permeability transition and cell death
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DOI：
10.1016/j.bbabio.2006.03.017
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发表时间：
2006-09-01
影响因子：
4.3
通讯作者：
Shimizu, Shigeomi
中科院分区：
文献类型：
--
作者：
Tsujimoto, Yoshihide;Nakagawa, Takashi;Shimizu, Shigeomi
线粒体是能量产生、Ca 2+稳态和细胞死亡的重要细胞器。近年来，线粒体在细胞凋亡和坏死中的作用受到了广泛关注。在凋亡和坏死性死亡中，线粒体膜通透性的增加被认为是关键事件之一，尽管详细的机制仍有待阐明。线粒体膜渗透性转变（MPT）是线粒体膜渗透性的Ca 2+依赖性增加，其导致Δ psi损失、线粒体肿胀和线粒体外膜破裂。NIPT被认为是在通道打开后发生的，该通道被称为渗透性转换孔（PTP），并且通道由电压依赖性阴离子通道（VDAC）、腺嘌呤核苷酸转运体（ANT）、亲环素D（Cyp D：线粒体肽基脯氨酰-顺式、反式异构酶）和其他分子组成。我们对缺乏Cyp D的小鼠的研究表明，它对MPT的发生至关重要，并且Cyp D依赖性NUT调节某些形式的坏死性细胞死亡，但不调节凋亡性死亡。我们还发现了两种抗凋亡蛋白。Bcl-2和Bcl-x（L）通过直接抑制VDAC活性来阻断NTPT。在这里，我们总结了MPT在细胞死亡中的作用。(c)2006 Elsevier B. V.保留所有权利。
Mitochondria are important organelles for energy production, Ca2+ homeostasis, and cell death. In recent years, the role of the mitochondria in both apoptotic and necrotic cell death has received much attention. In apoptotic and necrotic death, an increase of mitochondrial membrane permeability is considered to be one of the key events, although the detailed mechanism remains to be elucidated. The mitochondrial membrane permeability transition (MPT) is a Ca2+-dependent increase in the permeability of the mitochondrial membrane that leads to loss of Delta psi, mitochondrial swelling, and rupture of the outer mitochondrial membrane. The NIPT is thought to occur after the opening of a channel, which is termed the permeability transition pore (PTP) and putatively consists of the voltage-dependent anion channel (VDAC), the adenine nucleotide translocator (ANT), cyclophilin D (Cyp D: a mitochondrial peptidyl prolyl-cis, trans-isomerase), and other molecule(s). Our studies of mice lacking Cyp D have revealed that it is essential for occurrence of the MPT and that the Cyp D-dependent NUT regulates some forms of necrotic cell death, but not apoptotic death. We have also shown that two anti-apoptotic proteins. Bcl-2 and Bcl-x(L), block the NTPT by directly inhibition of VDAC activity. Here we summarize a role of the MPT in cell death. (c) 2006 Elsevier B.V. All rights reserved.