Bax/Bak promote sumoylation of DRP1 and its stable association with mitochondria during apoptotic cell death.
Bax/Bak promote sumoylation of DRP1 and its stable association with mitochondria during apoptotic cell death.
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DOI：
10.1083/jcb.200610042
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发表时间：
2007-05-07
期刊：
影响因子：
--
通讯作者：
McBride HM
中科院分区：
文献类型：
--
作者：
Wasiak S;Zunino R;McBride HM
动力蛋白相关蛋白1（DRP 1）在稳态线粒体分裂和凋亡过程中起重要作用。使用光漂白后的荧光恢复，我们证明在健康细胞中，黄色荧光蛋白（YFP）-DRP 1在细胞质和线粒体之间循环，半衰期为50 s。引人注目的是，在凋亡细胞死亡过程中，YFP-DRP 1经历了从快速回收到稳定膜结合的转变。细胞凋亡早期的快速循环期与Bax/巴克无关。然而，在Bax募集到线粒体膜之后但在线粒体膜电位丧失之前，YFP-DRP 1被锁定在膜上，导致不可检测的荧光恢复。DRP 1循环的第二阶段依赖于Bax/巴克的存在，但不依赖于hFis 1和线粒体片段化。与Bax激活相一致，我们检测到Bax/Bak-dependent刺激小泛素样修饰剂-1缀合到DRP 1，一种与DRP 1与线粒体膜的稳定关联相关的修饰。总之，这些数据表明，细胞凋亡机制调节细胞死亡过程中的DRP 1的生化特性。
Dynamin-related protein 1 (DRP1) plays an important role in mitochondrial fission at steady state and during apoptosis. Using fluorescence recovery after photobleaching, we demonstrate that in healthy cells, yellow fluorescent protein (YFP)–DRP1 recycles between the cytoplasm and mitochondria with a half-time of 50 s. Strikingly, during apoptotic cell death, YFP-DRP1 undergoes a transition from rapid recycling to stable membrane association. The rapid cycling phase that characterizes the early stages of apoptosis is independent of Bax/Bak. However, after Bax recruitment to the mitochondrial membranes but before the loss of mitochondrial membrane potential, YFP-DRP1 becomes locked on the membrane, resulting in undetectable fluorescence recovery. This second phase in DRP1 cycling is dependent on the presence of Bax/Bak but independent of hFis1 and mitochondrial fragmentation. Coincident with Bax activation, we detect a Bax/Bak-dependent stimulation of small ubiquitin-like modifier-1 conjugation to DRP1, a modification that correlates with the stable association of DRP1 with mitochondrial membranes. Altogether, these data demonstrate that the apoptotic machinery regulates the biochemical properties of DRP1 during cell death.
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