Mitochondria- and ER-associated actin are required for mitochondrial fusion.
Mitochondria- and ER-associated actin are required for mitochondrial fusion.
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线粒体和内质网相关肌动蛋白是线粒体融合所必需的。
DOI：
10.1101/2023.06.13.544768
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Germain,Marc
中科院分区：
文献类型：
--
作者：
Gatti,Priya;Schiavon,Cara;Manor,Uri;Germain,Marc
线粒体对细胞新陈代谢和信号传递至关重要。线粒体的活动受线粒体分裂和融合的调节，这是适当平衡代谢功能、在线粒体之间转移物质和移除有缺陷的线粒体所必需的。线粒体的分裂发生在线粒体-内质网(ER)的接触部位，需要肌动蛋白细丝的形成来驱动线粒体的收缩，并重新招募分裂蛋白Drp1。肌动蛋白在线粒体融合中的作用仍然完全不清楚。在这里，我们表明，阻止线粒体或内质网上的肌动蛋白聚合会破坏分裂和融合。我们发现融合而不是分裂依赖于Arp2/3，而分裂和融合都需要INF2依赖的肌动蛋白聚合。我们还表明，线粒体相关肌动蛋白在融合蛋白Mfn2之前标记融合位点。总之，我们的工作介绍了一种扰乱细胞器相关肌动蛋白的方法，并展示了肌动蛋白在线粒体融合中先前未知的作用。
Mitochondria are crucial for cellular metabolism and signalling. Mitochondrial activity is modulated by mitochondrial fission and fusion, which are required to properly balance metabolic functions, transfer material between mitochondria, and remove defective mitochondria. Mitochondrial fission occurs at mitochondria-endoplasmic reticulum (ER) contact sites, and requires the formation of actin filaments that drive mitochondrial constriction and the recruitment of the fission protein DRP1. The role of actin in mitochondrial fusion remains entirely unexplored. Here we show that preventing actin polymerisation on either mitochondria or the ER disrupts both fission and fusion. We show that fusion but not fission is dependent on Arp2/3, whereas both fission and fusion require INF2 formin-dependent actin polymerization. We also show that mitochondria-associated actin marks fusion sites prior to the fusion protein MFN2. Together, our work introduces a method for perturbing organelle-associated actin and demonstrates a previously unknown role for actin in mitochondrial fusion.