Garrido C, Galluzzi L, Brunet M, Puig P E, Didelot C, Kroemer G
INSERM U517, Faculty of Medicine and Pharmacy, F-21033 Dijon, France.
Cell Death Differ. 2006 Sep;13(9):1423-33. doi: 10.1038/sj.cdd.4401950. Epub 2006 May 5.
In healthy cells, cytochrome c (Cyt c) is located in the mitochondrial intermembrane/intercristae spaces, where it functions as an electron shuttle in the respiratory chain and interacts with cardiolipin (CL). Several proapoptotic stimuli induce the permeabilization of the outer membrane, facilitate the communication between intermembrane and intercristae spaces and promote the mobilization of Cyt c from CL, allowing for Cyt c release. In the cytosol, Cyt c mediates the allosteric activation of apoptosis-protease activating factor 1, which is required for the proteolytic maturation of caspase-9 and caspase-3. Activated caspases ultimately lead to apoptotic cell dismantling. Nevertheless, cytosolic Cyt c has been associated also to vital cell functions (i.e. differentiation), suggesting that its release not always occurs in an all-or-nothing fashion and that mitochondrial outer membrane permeabilization may not invariably lead to cell death. This review deals with the events involved in Cyt c release from mitochondria, with special attention to its regulation and final consequences.
在健康细胞中，细胞色素c（Cyt c）位于线粒体内膜/嵴间空间，在呼吸链中作为电子穿梭体发挥作用，并与心磷脂（CL）相互作用。几种促凋亡刺激可诱导外膜通透化，促进内膜和嵴间空间之间的通讯，并促进Cyt c从CL上解离，从而实现Cyt c释放。在细胞质中，Cyt c介导凋亡蛋白酶激活因子1的变构激活，这是半胱天冬酶-9和半胱天冬酶-3蛋白水解成熟所必需的。激活的半胱天冬酶最终导致凋亡细胞解体。然而，细胞质中的Cyt c也与重要的细胞功能（如分化）有关，这表明其释放并非总是全或无的方式，线粒体外膜通透化也不一定总是导致细胞死亡。本综述探讨了Cyt c从线粒体释放所涉及的事件，特别关注其调节和最终后果。
