Department of Physiology and Medical Physics, Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Oncogene. 2013 May 30;32(22):2703-11. doi: 10.1038/onc.2012.348. Epub 2012 Aug 6.
Mitochondria have been classically characterized as organelles with responsibility for cellular energy production in the form of ATP, but they are also the organelles through which apoptotic signaling occurs. Cell stress stimuli can result in outer membrane permeabilization, after which mitochondria release numerous proteins involved in apoptotic signaling, including cytochrome c, apoptosis-inducing factor, endonuclease G, Smac/DIABLO and Omi/HtrA2. Cell fate is determined by signaling through apoptotic proteins within the Bcl-2 (B-cell lymphoma 2) protein family, which converges on mitochondria. Many cancerous cells display abnormal levels of Bcl-2 protein family member expression that results in defective apoptotic signaling. Alterations in bioenergetic function also contribute to cancer as well as numerous other disorders. Recent evidence indicates that several pro-apoptotic proteins localized within mitochondria, as well as proteins within the Bcl-2 protein family, can influence mitochondrial bioenergetic function. This review focuses on the emerging roles of these proteins in the control of mitochondrial activity.
线粒体一直被经典地描述为细胞器，负责以 ATP 的形式产生细胞能量，但它们也是细胞凋亡信号发生的细胞器。细胞应激刺激可导致外膜通透性增加，随后线粒体释放许多参与细胞凋亡信号的蛋白质，包括细胞色素 c、凋亡诱导因子、内切核酸酶 G、Smac/DIABLO 和 Omi/HtrA2。细胞命运由 Bcl-2（B 细胞淋巴瘤 2）蛋白家族内的凋亡蛋白信号决定，这些蛋白汇聚在线粒体上。许多癌细胞显示出异常水平的 Bcl-2 蛋白家族成员表达，导致凋亡信号缺陷。生物能量功能的改变也会导致癌症和许多其他疾病。最近的证据表明，几种定位于线粒体的促凋亡蛋白以及 Bcl-2 蛋白家族内的蛋白质，可以影响线粒体的生物能量功能。本文综述了这些蛋白在控制线粒体活性中的新作用。
