Mitochondria, glutamate neurotoxicity and the death cascade.
Mitochondria, glutamate neurotoxicity and the death cascade.
复制标题
DOI：
10.1016/s0005-2728(98)00124-8
复制
发表时间：
1998-08
期刊：
影响因子：
--
通讯作者：
Mauricio Montal
中科院分区：
文献类型：
--
作者：
Mauricio Montal
本综述重点关注两个问题：线粒体在兴奋性毒性神经元死亡中的作用以及线粒体与细胞凋亡级联的联系。目的是强调线粒体通道对线粒体膜电位 Δψ 的调节作用，以及它们在决定神经元存活或死亡中的作用。一个假说的中心思想是，死亡抑制蛋白 Bcl-2 家族成员和启动子蛋白之间的蛋白质-蛋白质相互作用导致去极化电流的选择性消除，进而使 Δψ 崩溃并启动细胞死亡的不可逆途径。该模型考虑了 Bcl-2 家族蛋白二聚化或寡聚化的显着倾向，从而限制了伴侣分子在线粒体膜接触位点的定位。这里引用的基本原理是，通过一组协调一致的蛋白质-蛋白质相互作用，信息由特定的异二聚体交换，其中一个伙伴充当有毒蛋白质，第二个充当其解毒剂。该综述最后详细阐述了一个关于防止由细胞外信号触发的细胞破坏的细胞机制的推测模型，这些信号在从细菌到真核生物的分子设计中可能是保守的。
This review focuses on two questions: the role of mitochondria in excitotoxic neuronal death and the connection of mitochondria with the apoptotic death cascade. The goal is to highlight the regulatory role of mitochondrial channels on the mitochondrial membrane potential, Δψ, and their involvement in determining neuronal survival or death. A hypothesis is developed centered on the notion that protein–protein interactions between members of the Bcl-2 family of death suppressor and promoter proteins lead to the selective elimination of depolarizing currents that, in turn, collapse Δψ and set in motion the irreversible pathway of cell death. The model considers the remarkable propensity of Bcl-2 family proteins to dimerize or oligomerize and thereby restrict the localization of partner molecules to mitochondrial membrane contact sites. The fundamental principle invoked here is that through a concerted set of protein–protein interactions, information is exchanged by specific heterodimers, one of the partners acting as a toxic protein and the second as its antidote. The review concludes with the elaboration of a speculative model about cellular mechanisms for the prevention of cell destruction as triggered by extracellular signals which may be conserved in its molecular design from bacteria to eukaryotes.