Kroemer G
Centre National de la Recherche Scientifique-UPR420, B.P.8, F-94801 Villejuif, France.
Cell Death Differ. 1997 Aug;4(6):443-56. doi: 10.1038/sj.cdd.4400266.
Recent evidence indicates that a profound alteration in mitochondrial function constitutes an obligatory early event of the apoptotic process. The molecular mechanism accounting for this alteration is mitochondrial permeability transition (PT). PT is both sufficient and necessary for apoptosis to occur. Experiments performed in cell-free systems of apoptosis demonstrate that mitochondria undergoing PT release protease activators that can trigger nuclear manifestations of apoptosis. Bcl-2 and its homologs are endogenous regulators of PT. It appears that some types of necrosis, those inhibited by Bcl-2, involve PT. If PT is a rate-limiting event of both apoptosis and necrosis, then downstream events including caspase activation and the bioenergetic consequences of PT must determine the choice between both modes of cell death. PT without caspase activation would cause necrosis. These findings have important implications for the comprehension of the apoptotic process, for the dichotomy between apoptosis and necrosis, and for the phylogeny of programmed cell death. Apoptosis may have evolved together with the endosymbiotic incorporation of aerobic bacteria (the precursors of mitochondria) into ancestral unicellular eukaryotes.
最近的证据表明，线粒体功能的深刻改变是凋亡过程中必不可少的早期事件。解释这种改变的分子机制是线粒体通透性转换（PT）。PT对于凋亡的发生既是充分的也是必要的。在无细胞凋亡系统中进行的实验表明，经历PT的线粒体释放出能够触发凋亡核表现的蛋白酶激活剂。Bcl-2及其同源物是PT的内源性调节因子。似乎某些类型的坏死，即那些被Bcl-2抑制的坏死，涉及PT。如果PT是凋亡和坏死的限速事件，那么包括半胱天冬酶激活和PT的生物能量后果在内的下游事件必须决定两种细胞死亡模式之间的选择。没有半胱天冬酶激活的PT会导致坏死。这些发现对于理解凋亡过程、凋亡与坏死之间的二分法以及程序性细胞死亡的系统发育具有重要意义。凋亡可能与需氧细菌（线粒体的前体）内共生整合到原始单细胞真核生物中一起进化而来。
