Multiple dynamin family members collaborate to drive mitochondrial division.
Multiple dynamin family members collaborate to drive mitochondrial division.
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DOI：
10.1038/nature20555
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发表时间：
2016-12-01
期刊：
影响因子：
64.8
通讯作者：
Voeltz GK
中科院分区：
文献类型：
--
作者：
Lee JE;Westrate LM;Wu H;Page C;Voeltz GK
线粒体不能从头产生；它们必须生长、复制基因组并分裂，以便在有丝分裂时遗传给每个子细胞。线粒体分裂是一种结构上的挑战，需要大量的膜形态重塑。尽管不同生物的分裂因子不同，但对多个收缩步骤和动力蛋白相关蛋白（酵母中的Drp1， Dnm1）的需求是保守的。在哺乳动物细胞中，线粒体分裂已被证明至少有两个连续的收缩步骤：内质网（ER）和肌动蛋白协同产生适合Drp1组装的缩窄；2. Drp1进一步收缩膜，直到发生裂变。然而，体外实验表明，Drp1本身不具备完成膜裂变的动态范围。与Drp1相反，神经元特异性的经典动力蛋白-1 （Dyn1）已被证明在更窄的脂质谱上聚集，并在GTP水解时促进自发膜裂变。在这里，我们发现普遍表达的经典动力蛋白-2 （Dyn2）是线粒体分裂机制的基本组成部分。活细胞和电子显微镜的结合显示，Dyn2与Drp1协同工作，协调导致分裂的连续收缩事件。我们的工作强调了Drp1的生物物理局限性，并将具有固有膜裂变特性的Dyn2定位在线粒体分裂的最后一步。
Mitochondria cannot be generated de novo; they must grow, replicate their genome, and divide in order to be inherited to each daughter cell during mitosis. Mitochondrial division is a structural challenge that requires a massive remodeling of membrane morphology . Although division factors differ across organisms, the need for multiple constriction steps and a dynamin-related protein (Drp1, Dnm1 in yeast) has been conserved . In mammalian cells, mitochondrial division has been shown to proceed with at least two sequential constriction steps: 1. endoplasmic reticulum (ER) and actin collaborate to generate constrictions suitable for Drp1 assembly; 2. Drp1 further constricts membranes until fission occurs . However, in vitro experiments argue that Drp1 does not have the dynamic range to complete membrane fission per se . In contrast to Drp1, the neuronal-specific classical Dynamin-1 (Dyn1) has been shown to assemble on narrower lipid profiles and facilitates spontaneous membrane fission upon GTP hydrolysis . Here we discovered that the ubiquitously-expressed classical Dynamin-2 (Dyn2) is a fundamental component of the mitochondrial division machinery. A combination of live-cell and electron microscopy reveals that Dyn2 works in concert with Drp1 to orchestrate sequential constriction events leading up to division. Our work underscores the biophysical limitations of Drp1 and positions Dyn2, which has intrinsic membrane fission properties, at the final step of mitochondrial division.
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DOI：
10.1083/jcb.201508099
发表时间：
2016-02-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Otera H;Miyata N;Kuge O;Mihara K
通讯作者：
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影响因子：
21.3
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影响因子：
12.4
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DOI：
10.1073/pnas.1407163112
发表时间：
2015-03-03
影响因子：
11.1
作者：
Purkanti, Ramya;Thattai, Mukund
通讯作者：
Thattai, Mukund
DOI：
10.1093/jmicro/dfs001
发表时间：
2012-04-01
期刊：
JOURNAL OF ELECTRON MICROSCOPY
影响因子：
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作者：
Kim, Hyun-Wook;Oh, Seung Hak;Rhyu, Im Joo
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