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Dynamin-related protein 1 has membrane constricting and severing abilities sufficient for mitochondrial and peroxisomal fission.
Nature Communications ( IF 16.6 ) Pub Date : 2018-12-07 , DOI: 10.1038/s41467-018-07543-w
Sukrut C Kamerkar 1 , Felix Kraus 2 , Alice J Sharpe 2 , Thomas J Pucadyil 1 , Michael T Ryan 2
Affiliation  

Dynamin-related protein 1 (Drp1) is essential for mitochondrial and peroxisomal fission. Recent studies propose that Drp1 does not sever but rather constricts mitochondrial membranes allowing dynamin 2 (Dnm2) to execute final scission. Here, we report that unlike Drp1, Dnm2 is dispensable for peroxisomal and mitochondrial fission, as these events occurred in Dnm2 knockout cells. Fission events were also observed in mouse embryonic fibroblasts lacking Dnm1, 2 and 3. Using reconstitution experiments on preformed membrane tubes, we show that Drp1 alone both constricts and severs membrane tubes. Scission required the membrane binding, self-assembling and GTPase activities of Drp1 and occurred on tubes up to 250 nm in radius. In contrast, Dnm2 exhibited severely restricted fission capacity with occasional severing of tubes below 50 nm in radius. We conclude that Drp1 has both membrane constricting and severing abilities and is the dominant dynamin performing mitochondrial and peroxisomal fission.

中文翻译:

Dynamin 相关蛋白 1 具有足以进行线粒体和过氧化物酶体裂变的膜收缩和切断能力。

动力相关蛋白 1 (Drp1) 对线粒体和过氧化物酶体裂变至关重要。最近的研究表明,Drp1 不会切断而是收缩线粒体膜,从而允许 dynamin 2 (Dnm2) 执行最终断裂。在这里,我们报告说,与 Drp1 不同,Dnm2 对于过氧化物酶体和线粒体裂变是可有可无的,因为这些事件发生在 Dnm2 敲除细胞中。在缺乏 Dnm1、2 和 3 的小鼠胚胎成纤维细胞中也观察到裂变事件。使用预制膜管的重组实验,我们表明单独的 Drp1 既可以收缩也可以切断膜管。分裂需要 Drp1 的膜结合、自组装和 GTPase 活性,并且发生在半径高达 250 nm 的管上。相比之下,Dnm2 表现出严重受限的裂变能力,偶尔会切断半径低于 50 nm 的管。
更新日期:2018-12-07
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