Arf6-driven cell invasion is intrinsically linked to TRAK1-mediated mitochondrial anterograde trafficking to avoid oxidative catastrophe.
Arf6-driven cell invasion is intrinsically linked to TRAK1-mediated mitochondrial anterograde trafficking to avoid oxidative catastrophe.
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DOI：
10.1038/s41467-018-05087-7
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发表时间：
2018-07-11
影响因子：
16.6
通讯作者：
Sabe H
中科院分区：
文献类型：
--
作者：
Onodera Y;Nam JM;Horikawa M;Shirato H;Sabe H
线粒体在细胞运动过程中动态地改变其亚细胞定位，尽管潜在的机制在很大程度上仍然难以捉摸。小分子GTP酶Arf6及其涉及AMAP1的信号通路通过整合素循环促进细胞侵袭。在这里，我们发现Arf6-AMAP1通路促进了线粒体的顺行运输。阻断Arf6途径会导致线粒体聚集在微管组织中心附近，从而诱导有害的活性氧(ROS)的产生，这可能是通过线粒体ROS诱导的ROS释放类机制实现的。基于Arf6的途径促进ILK到焦点粘连的定位，以阻止控制线粒体逆行运输的RhoT1-TRAK2关联。阻断RhoT1-TRAK1机制，而不是RhoT1-TRAK2，会损害细胞的侵袭，但不会损害细胞的二维随机迁移。弱或非侵袭性细胞不显著地表达TRAK蛋白，而它们清楚地表达它们的mRNAs。我们的结果发现了细胞运动和线粒体动力学之间的一种新的关联，这种关联是侵袭性的，对于避免有害的ROS产生是必要的。线粒体的亚细胞定位在迁移过程中受到动态调节。在这里，作者证明了Arf6-AMAP1依赖的ILK在局灶性粘连处的定位减少了线粒体在迁移细胞中的逆行运输，并防止了线粒体聚集和有害的ROS产生。
Mitochondria dynamically alter their subcellular localization during cell movement, although the underlying mechanisms remain largely elusive. The small GTPase Arf6 and its signaling pathway involving AMAP1 promote cell invasion via integrin recycling. Here we show that the Arf6–AMAP1 pathway promote the anterograde trafficking of mitochondria. Blocking the Arf6-based pathway causes mitochondrial aggregation near the microtubule-organizing center, and subsequently induces detrimental reactive oxygen species (ROS) production, likely via a mitochondrial ROS-induced ROS release-like mechanism. The Arf6-based pathway promotes the localization of ILK to focal adhesions to block RhoT1–TRAK2 association, which controls mitochondrial retrograde trafficking. Blockade of the RhoT1–TRAK1 machinery, rather than RhoT1–TRAK2, impairs cell invasion, but not two-dimensional random cell migration. Weakly or non-invasive cells do not notably express TRAK proteins, whereas they clearly express their mRNAs. Our results identified a novel association between cell movement and mitochondrial dynamics, which is specific to invasion and is necessary for avoiding detrimental ROS production. Mitochondria subcellular localization is dynamically regulated during migration. Here, the authors show that Arf6–AMAP1 dependent ILK localization at focal adhesions reduces mitochondrial retrograde trafficking in migratory cells and prevents mitochondrial aggregation and detrimental ROS production.
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影响因子：
6.4
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Tsuruo, T
DOI：
10.1073/pnas.1500722112
发表时间：
2015-07-14
影响因子：
11.1
作者：
Caino, M. Cecilia;Ghosh, Jagadish C.;Altieri, Dario C.
通讯作者：
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