Mitochondrial intermembrane junctional complexes and their role in cell death
Mitochondrial intermembrane junctional complexes and their role in cell death
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DOI：
10.1111/j.1469-7793.2000.00011.x
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发表时间：
2000-11-15
影响因子：
5.5
通讯作者：
Crompton, M
中科院分区：
文献类型：
--
作者：
Crompton, M
包含电压依赖性阴离子通道（外膜）、腺嘌呤核苷酸移位酶（内膜）和亲环蛋白-D（基质）的线粒体复合物在内膜和外膜之间的接触位点组装。在与缺血和再灌注相关的病理条件下，连接复合物“变形”成渗透性转换（PT）孔，其可以瞬时打开，允许低M-r溶质自由渗透穿过内膜。这可能是缺血和再灌注致死性细胞损伤发病机制中的关键步骤。此外，有人认为，孔开放的程度可能是一个重要的决定因素的相对程度的细胞凋亡和坏死在这些条件下。此外，线粒体是Pax和Bcl-2家族的其他凋亡调节蛋白的主要作用位点。这些蛋白质控制细胞凋亡信号通路中的线粒体扩增环，其中细胞色素c和线粒体膜间隙的其他促凋亡蛋白质被释放到细胞溶质中。有迹象表明，连接复合物，或其组分，也可能介导Bax的作用，但在某种程度上，不涉及PT孔的形成。
A mitochondrial complex comprising the voltage-dependent anion channel (outer membrane), the adenine nucleotide translocase (inner membrane) and cyclophilin-D (matrix) assembles at contact sites between the inner and outer membranes. Under pathological conditions associated with ischaemia and reperfusion the junctional complex 'deforms' into the permeability transition (PT) pore, which can open transiently, allowing free permeation of low M-r solutes across the inner membrane. This may be a critical step in the pathogenesis of lethal cell injury in ischaemia and reperfusion. Moreover, it is argued, the degree of pore opening may be an important determinant of the relative extent of apoptosis and necrosis under these conditions. In addition, mitochondria are the major sites of action of Pax and other apoptotic regulatory proteins of the Bcl-2 family. These proteins control a mitochondrial amplificatory loop in the apoptotic signalling pathway in which cytochrome c and other apoptogenic proteins of the mitochondrial intermembrane space are released into the cytosol. There are indications that the junctional complex, or components of it, may also mediate the action of Bax, but in a way that does not involve PT pore formation.