The AAA+ ATPase ATAD3A Controls Mitochondrial Dynamics at the Interface of the Inner and Outer Membranes
The AAA+ ATPase ATAD3A Controls Mitochondrial Dynamics at the Interface of the Inner and Outer Membranes
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DOI：
10.1128/mcb.00007-10
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发表时间：
2010-04-15
影响因子：
5.3
通讯作者：
Baudier, Jacques
中科院分区：
文献类型：
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作者：
Gilquin, Benoit;Taillebourg, Emmanuel;Baudier, Jacques
外膜(OM)和内膜(IM)组分之间的动态相互作用控制着许多关键的线粒体功能，如代谢产物的通道和协调的分裂和融合。在这里，我们发现线粒体AAA(+)ATPase蛋白ATAD3A是多细胞真核生物特有的，是这些相互作用的参与者。N端域与OM相互作用。一个中央跨膜片段(TMS)将蛋白质锚定在IM中，并将C-末端的AAA(+)ATPase结构域定位在基质中。在果蝇和人类类固醇生成细胞系中的失效研究表明，ATAD3A是正常细胞生长和接触部位胆固醇输送所必需的。利用显性-负性突变体，包括一个有缺陷的ATP结合突变体和一个截短50个氨基酸的N末端突变体，我们证明了ATAD3A调节细胞分裂机制所感知的线粒体OM和IM之间的动态相互作用。ATAD3A影响线粒体基本功能和组织的能力表明，它在调节多细胞生物体的线粒体动力学和细胞功能方面具有独特的性质。
Dynamic interactions between components of the outer (OM) and inner (IM) membranes control a number of critical mitochondrial functions such as channeling of metabolites and coordinated fission and fusion. We identify here the mitochondrial AAA(+) ATPase protein ATAD3A specific to multicellular eukaryotes as a participant in these interactions. The N-terminal domain interacts with the OM. A central transmembrane segment (TMS) anchors the protein in the IM and positions the C-terminal AAA(+) ATPase domain in the matrix. Invalidation studies in Drosophila and in a human steroidogenic cell line showed that ATAD3A is required for normal cell growth and cholesterol channeling at contact sites. Using dominant-negative mutants, including a defective ATP-binding mutant and a truncated 50-amino-acid N-terminus mutant, we showed that ATAD3A regulates dynamic interactions between the mitochondrial OM and IM sensed by the cell fission machinery. The capacity of ATAD3A to impact essential mitochondrial functions and organization suggests that it possesses unique properties in regulating mitochondrial dynamics and cellular functions in multicellular organisms.