Mitofusin 2 tethers endoplasmic reticulum to mitochondria
Mitofusin 2 tethers endoplasmic reticulum to mitochondria
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DOI：
10.1038/nature07534
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发表时间：
2008-12-04
期刊：
影响因子：
64.8
通讯作者：
Scorrano, Luca
中科院分区：
文献类型：
--
作者：
de Brito, Olga Martins;Scorrano, Luca
内质网（ER）和线粒体之间的并置是一种常见的结构特征，为Ca（2+）信号传导过程中的相互通讯提供了物理基础;然而，控制这种相互作用的分子机制尚不清楚。在这里，我们表明，线粒体融合蛋白2，线粒体动力蛋白相关蛋白突变的遗传性运动神经病夏科-玛丽-牙齿IIa型，是丰富的ER -线粒体界面。在小鼠胚胎成纤维细胞和HeLa细胞中的丝裂融合蛋白2的消融或沉默破坏了ER形态并放松了ER -线粒体相互作用，从而降低了响应于产生肌醇-1，4，5-三磷酸的刺激的线粒体Ca（2+）摄取的效率。体外试验以及遗传和生物化学证据支持这样的模型，其中ER上的线粒体融合蛋白2通过与线粒体表面上的线粒体融合蛋白1或2形成同型和异型复合物来桥接两个细胞器。因此，mitofusin 2将ER拴在线粒体上，这是有效的线粒体Ca（2+）摄取所需的并置。
Juxtaposition between endoplasmic reticulum ( ER) and mitochondria is a common structural feature, providing the physical basis for intercommunication during Ca(2+) signalling; yet, the molecular mechanisms controlling this interaction are unknown. Here we show that mitofusin 2, a mitochondrial dynamin- related protein mutated in the inherited motor neuropathy Charcot - Marie - Tooth type IIa, is enriched at the ER - mitochondria interface. Ablation or silencing of mitofusin 2 in mouse embryonic fibroblasts and HeLa cells disrupts ER morphology and loosens ER - mitochondria interactions, thereby reducing the efficiency of mitochondrial Ca(2+) uptake in response to stimuli that generate inositol-1,4,5-trisphosphate. An in vitro assay as well as genetic and biochemical evidences support a model in which mitofusin 2 on the ER bridges the two organelles by engaging in homotypic and heterotypic complexes with mitofusin 1 or 2 on the surface of mitochondria. Thus, mitofusin 2 tethers ER to mitochondria, a juxtaposition required for efficient mitochondrial Ca(2+) uptake.