Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors
Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors
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DOI：
10.1038/nchembio727
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发表时间：
2005-09-01
影响因子：
14.8
通讯作者：
Borisenko, GG
中科院分区：
文献类型：
--
作者：
Kagan, VE;Tyurin, VA;Borisenko, GG
程序性死亡（细胞凋亡）在受损或不需要的细胞中开启，以确保它们清洁和安全的自我消除。最初的细胞凋亡事件在线粒体中协调，由此几种促细胞凋亡因子，包括细胞色素c，被释放到细胞溶质中以触发半胱天冬酶级联。释放机制包括B-细胞/淋巴瘤2家族蛋白与线粒体特异性磷脂心磷脂的相互作用，以引起线粒体外膜的透化。使用氧化脂质组学，我们发现心磷脂是线粒体中唯一在凋亡过程中经历早期氧化的磷脂。氧化反应由心磷脂结合细胞色素c的心磷脂特异性过氧化物酶活性催化。在一个以前未描述的步骤，在细胞凋亡中，我们表明，氧化心磷脂是所需的释放促凋亡因子。这些结果提供了深入了解活性氧在触发细胞死亡途径中的作用，并描述了细胞色素c在半胱天冬酶激活前的早期作用。
Programmed death (apoptosis) is turned on in damaged or unwanted cells to secure their clean and safe self-elimination. The initial apoptotic events are coordinated in mitochondria, whereby several proapoptotic factors, including cytochrome c, are released into the cytosol to trigger caspase cascades. The release mechanisms include interactions of B-cell/lymphoma 2 family proteins with a mitochondria-specific phospholipid, cardiolipin, to cause permeabilization of the outer mitochondrial membrane. Using oxidative lipidomics, we showed that cardiolipin is the only phospholipid in mitochondria that undergoes early oxidation during apoptosis. The oxidation is catalyzed by a cardiolipin-specific peroxidase activity of cardiolipin-bound cytochrome c. In a previously undescribed step in apoptosis, we showed that oxidized cardiolipin is required for the release of proapoptotic factors. These results provide insight into the role of reactive oxygen species in triggering the cell-death pathway and describe an early role for cytochrome c before caspase activation.