In addition to the established role of the mitochondria in energy metabolism, regulation of cell death has emerged as a second major function of these organelles. This seems to be intimately linked to their generation of reactive oxygen species (ROS), which have been implicated in mtDNA mutations, aging, and cell death. Mitochondrial regulation of apoptosis occurs by mechanisms, which have been conserved through evolution. Thus, many lethal agents target the mitochondria and cause release of cytochrome c and other pro-apoptotic proteins into the cytoplasm. Cytochrome c release is initiated by the dissociation of the hemoprotein from its binding to the inner mitochondrial membrane. Oxidation of cardiolipin reduces cytochrome c binding and increases the level of soluble cytochrome c in the intermembrane space. Subsequent release of the hemoprotein occurs by pore formation mediated by pro-apoptotic Bcl-2 family proteins, or by Ca(2+) and ROS-triggered mitochondrial permeability transition, although the latter pathway might be more closely associated with necrosis. Taken together, these findings have placed the mitochondria in the focus of current cell death research.

中文翻译：

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线粒体氧化应激：对细胞死亡的影响。

除了线粒体在能量代谢中的确定作用外，调节细胞死亡已成为这些细胞器的第二主要功能。这似乎与它们产生活性氧（ROS）密切相关，后者与mtDNA突变，衰老和细胞死亡有关。线粒体对细胞凋亡的调节是通过机制进行的，这些机制通过进化得以保持。因此，许多致死剂靶向线粒体，并导致细胞色素c和其他促凋亡蛋白释放到细胞质中。细胞色素c的释放是由血红蛋白从其与线粒体内膜的结合中解离而引发的。心磷脂的氧化减少细胞色素c的结合并增加膜间空间中可溶性细胞色素c的水平。血红蛋白的后续释放是通过促凋亡Bcl-2家族蛋白或Ca（2+）和ROS触发的线粒体通透性转变介导的孔形成而发生的，尽管后者可能与坏死更紧密相关。综上所述，这些发现使线粒体成为当前细胞死亡研究的重点。