The BCL-2-like protein CED-9 of C. elegans promotes FZO-1/Mfn1,2- and EAT-3/Opa1-dependent mitochondrial fusion.

The BCL-2-like protein CED-9 of C. elegans promotes FZO-1/Mfn1,2- and EAT-3/Opa1-dependent mitochondrial fusion.
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DOI:
10.1083/jcb.200905070
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发表时间:
2009-08-24
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Conradt B
Conradt B
中科院分区:
其他
文献类型:
--
作者:
Rolland SG;Lu Y;David CN;Conradt B

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哺乳动物动力蛋白相关的鸟苷三磷酸酶Mfn1、2和OPA1是线粒体融合所必需的。然而,他们的活动是如何控制和协调的,在很大程度上是未知的。我们提供的数据表明,bcl2样蛋白CED-9在线虫线粒体融合的控制中发挥作用。我们证明CED-9可以促进线粒体外膜和内膜的完全融合。我们还表明,这种融合依赖于线虫Mfn1,2同源物FZO-1和线虫OPA1同源物EAT-3。此外,我们发现CED-9在体内与FZO-1发生物理相互作用,CED-9与FZO-1相互作用的能力对于其导致线粒体融合的能力是重要的。CED-9诱导的线粒体融合不是在胚胎发生期间或在肌肉细胞中维持线粒体形态所必需的,至少在正常条件下和在没有应激的情况下是这样。因此,我们认为BCL-2样CED-9通过FZO-1/Mfn1,2和EAT-3/OPA1促进线粒体融合,以响应特定的细胞信号。
The mammalian dynamin-related guanosine triphosphatases Mfn1,2 and Opa1 are required for mitochondrial fusion. However, how their activities are controlled and coordinated is largely unknown. We present data that implicate the BCL-2–like protein CED-9 in the control of mitochondrial fusion in Caenorhabditis elegans. We demonstrate that CED-9 can promote complete mitochondrial fusion of both the outer and inner mitochondrial membrane. We also show that this fusion is dependent on the C. elegans Mfn1,2 homologue FZO-1 and the C. elegans Opa1 homologue EAT-3. Furthermore, we show that CED-9 physically interacts with FZO-1 in vivo and that the ability of CED-9 to interact with FZO-1 is important for its ability to cause mitochondrial fusion. CED-9–induced mitochondrial fusion is not required for the maintenance of mitochondrial morphology during embryogenesis or in muscle cells, at least under normal conditions and in the absence of stress. Therefore, we propose that the BCL-2–like CED-9 acts through FZO-1/Mfn1,2 and EAT-3/Opa1 to promote mitochondrial fusion in response to specific cellular signals.
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