The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice.
The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice.
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DOI：
10.1083/jcb.200903065
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发表时间：
2009-09-21
期刊：
影响因子：
--
通讯作者：
Sesaki H
中科院分区：
文献类型：
--
作者：
Wakabayashi J;Zhang Z;Wakabayashi N;Tamura Y;Fukaya M;Kensler TW;Iijima M;Sesaki H
脑特异性Drp1基因敲除小鼠表明，Drp1介导的细胞器分裂对发育、线粒体形态发生和细胞凋亡很重要。与动力蛋白相关的鸟苷三磷酸酶Drp1介导线粒体和过氧化物酶体的分裂。为了了解Drp1在体内的功能，我们生成了Drp1的完整的、组织特异性的小鼠基因敲除。drp1缺失小鼠在胚胎第11.5天死亡。这种胚胎致死不太可能是由总能量剥夺引起的，因为drp1缺失的细胞显示出正常的细胞内三磷酸腺苷水平。为了支持Drp1在细胞器分裂中的作用，在Drp1缺失的胚胎成纤维细胞中，线粒体形成了广泛的网络，过氧化物酶体被拉长。脑特异性Drp1消融引起小脑发育缺陷，其中浦肯野细胞含有很少的巨型线粒体，而不是对照细胞中观察到的许多短管线粒体。此外，在体内，drp1缺失的胚胎在神经管形成过程中未能发生发育调节的细胞凋亡。然而，在体外实验中，Drp1缺失的胚胎成纤维细胞对凋亡刺激的反应正常，这表明Drp1的凋亡功能取决于生理信号。这些发现清楚地证明了drp1介导的细胞器分裂在小鼠中的生理重要性。
Brain-specific Drp1 knockout mice demonstrate that Drp1-mediated organelle division is important for development, mitochondrial morphogenesis, and apoptosis. The dynamin-related guanosine triphosphatase Drp1 mediates the division of mitochondria and peroxisomes. To understand the in vivo function of Drp1, complete and tissue-specific mouse knockouts of Drp1 were generated. Drp1-null mice die by embryonic day 11.5. This embryonic lethality is not likely caused by gross energy deprivation, as Drp1-null cells showed normal intracellular adenosine triphosphate levels. In support of the role of Drp1 in organelle division, mitochondria formed extensive networks, and peroxisomes were elongated in Drp1-null embryonic fibroblasts. Brain-specific Drp1 ablation caused developmental defects of the cerebellum in which Purkinje cells contained few giant mitochondria instead of the many short tubular mitochondria observed in control cells. In addition, Drp1-null embryos failed to undergo developmentally regulated apoptosis during neural tube formation in vivo. However, Drp1-null embryonic fibroblasts have normal responses to apoptotic stimuli in vitro, suggesting that the apoptotic function of Drp1 depends on physiological cues. These findings clearly demonstrate the physiological importance of Drp1-mediated organelle division in mice.
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影响因子：
11.8
作者：
Goyal, Gaurav;Fell, Brennan;Sarin, Apurva;Youle, Richard J.;Sriram, V.
通讯作者：
Sriram, V.
影响因子：
21.3
作者：
Bleazard, W;McCaffery, JM;Shaw, JM
通讯作者：
Shaw, JM
影响因子：
11.4
作者：
Germain, M;Mathai, JP;Shore, GC
通讯作者：
Shore, GC
影响因子：
11.8
作者：
Cerveny, Kara L.;Studer, Seth L.;Sesaki, Hiromi
通讯作者：
Sesaki, Hiromi
DOI：
10.1083/jcb.200211046
发表时间：
2003-01-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen H;Detmer SA;Ewald AJ;Griffin EE;Fraser SE;Chan DC
通讯作者：
Chan DC