Interchangeable adaptors regulate mitochondrial dynamin assembly for membrane scission
Interchangeable adaptors regulate mitochondrial dynamin assembly for membrane scission
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DOI：
10.1073/pnas.1300855110
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发表时间：
2013-04-09
影响因子：
11.1
通讯作者：
Shaw, Janet M.
中科院分区：
文献类型：
--
作者：
Koirala, Sajjan;Guo, Qian;Shaw, Janet M.
线粒体分裂由动力蛋白相关的GTP酶Dnm 1/Drp 1（酵母/哺乳动物）介导，其在线粒体上的收缩位点周围形成螺旋。需要额外的膜相关衔接蛋白（Fis 1、Mdv 1、Mff和MiD）将这些GTPases从细胞质募集到线粒体表面。这些衔接子是否参与GT3募集和膜断裂尚不清楚。在这里，我们使用的酵母菌株缺乏所有的裂变蛋白，以确定足够的线粒体裂变的GTP酶和衔接子的最小组合。尽管Fis 1不适于分裂，但膜锚定的Mdv 1、Mff或MiD与其各自的GTP酶单独配对足以分裂线粒体。除了它们在Drp 1膜募集中的作用之外，MiD在体外与Drp 1共组装。所得的杂聚物采用了一个显着不同的结构，具有较窄的直径比Drp 1均聚物在隔离组装。这一结果表明，衔接蛋白改变了线粒体动力蛋白GTdR聚合物的结构，可以促进膜收缩和切断活性的方式。
Mitochondrial fission is mediated by the dynamin-related GTPases Dnm1/Drp1 (yeast/mammals), which form spirals around constricted sites on mitochondria. Additional membrane-associated adaptor proteins (Fis1, Mdv1, Mff, and MiDs) are required to recruit these GTPases from the cytoplasm to the mitochondrial surface. Whether these adaptors participate in both GTPase recruitment and membrane scission is not known. Here we use a yeast strain lacking all fission proteins to identify the minimal combinations of GTPases and adaptors sufficient for mitochondrial fission. Although Fis1 is dispensable for fission, membrane-anchored Mdv1, Mff, or MiDs paired individually with their respective GTPases are sufficient to divide mitochondria. In addition to their role in Drp1 membrane recruitment, MiDs coassemble with Drp1 in vitro. The resulting heteropolymer adopts a dramatically different structure with a narrower diameter than Drp1 homopolymers assembled in isolation. This result demonstrates that an adaptor protein alters the architecture of a mitochondrial dynamin GTPase polymer in a manner that could facilitate membrane constriction and severing activity.