Coincident Phosphatidic Acid Interaction Restrains Drp1 in Mitochondrial Division.
Coincident Phosphatidic Acid Interaction Restrains Drp1 in Mitochondrial Division.
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DOI：
10.1016/j.molcel.2016.08.013
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发表时间：
2016-09-15
期刊：
影响因子：
16
通讯作者：
Sesaki, Hiromi
中科院分区：
文献类型：
--
作者：
Adachi, Yoshihiro;Itoh, Kie;Yamada, Tatsuya;Cerveny, Kara L.;Suzuki, Takamichi L.;Macdonald, Patrick;Frohman, Michael A.;Ramachandran, Rajesh;Iijima, Miho;Sesaki, Hiromi
线粒体通过分裂来控制其大小、分布、周转和功能。动力蛋白相关蛋白（Drp1）是一种重要的机械化学GTdR，在线粒体分裂过程中驱动收缩。一般认为，线粒体分裂在Drp1向线粒体的募集及其寡聚化成分裂装置期间受到调节。在这里，我们报告了一个不可预见的机制，调节线粒体分裂一致的相互作用Drp1与头基和酰基链的磷脂。Drp1通过渗透到膜的疏水核心来识别磷脂酸（PA）的头基和另一种磷脂的两个饱和酰基链。双磷脂相互作用抑制Drp1通过抑制寡聚化刺激的GTP水解，促进膜收缩。此外，一种产生PA的磷脂酶MitoPLD结合Drp1，在分裂器附近创造了一个富含PA的微环境。因此，PA在形成分割装置之后控制Drp1的激活。
Mitochondria divide to control their size, distribution, turnover and function. Dynamin-related protein (Drp1) is a critical mechanochemical GTPase that drives constriction during mitochondrial division. It is generally believed that mitochondrial division is regulated during recruitment of Drp1 to mitochondria and its oligomerization into a division apparatus. Here, we report an unforeseen mechanism that regulates mitochondrial division by coincident interactions of Drp1 with the headgroup and acyl chains of phospholipids. Drp1 recognizes the headgroup of phosphatidic acid (PA) and two saturated acyl chains of another phospholipid by penetrating into the hydrophobic core of the membrane. The dual phospholipid interactions restrain Drp1 via inhibition of oligomerization-stimulated GTP hydrolysis that promotes membrane constriction. Moreover, a PA-producing phospholipase, MitoPLD, binds Drp1, creating a PA-rich microenvironment in the vicinity of a division apparatus. Thus, PA controls the activation of Drp1 after the formation of the division apparatus.
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作者：
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