Mitochondria Associate with P-bodies and Modulate MicroRNA-mediated RNA Interference
Mitochondria Associate with P-bodies and Modulate MicroRNA-mediated RNA Interference
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DOI：
10.1074/jbc.m111.240259
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发表时间：
2011-07-08
影响因子：
4.8
通讯作者：
Weil, Dominique
中科院分区：
文献类型：
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作者：
Huang, Lue;Mollet, Stephanie;Weil, Dominique
p小体是细胞质颗粒，与mRNA衰变、mRNA储存和RNA干扰（RNAi）有关。已知它们与应激细胞中的应激颗粒和晚期核内体相互作用。在这里，我们报告了p小体也与线粒体相互作用，如前所述的生殖细胞中p小体相关颗粒。这种相互作用是动态的，因为大多数p体在3分钟的间隔内至少与线粒体接触一次，持续时间约为18秒。这种关联需要一个完整的微管网络。p体的耗竭似乎不影响线粒体，也不影响线粒体与p体接触所需的活性。然而，线粒体失活导致mirna介导的RNAi效率大幅降低，sirna介导的RNAi效率降低程度较小。该缺陷发生在主动RISC的组装过程中，与p -体的内源性Ago2的特定脱位有关。我们的研究揭示了RNAi缺陷可能涉及线粒体缺陷的病理。
P-bodies are cytoplasmic granules that are linked to mRNA decay, mRNA storage, and RNA interference (RNAi). They are known to interact with stress granules in stressed cells, and with late endosomes. Here, we report that P-bodies also interact with mitochondria, as previously described for P-body-related granules in germ cells. The interaction is dynamic, as a large majority of P-bodies contacts mitochondria at least once within a 3-min interval, and for about 18 s. This association requires an intact microtubule network. The depletion of P-bodies does not seem to affect mitochondria, nor the mitochondrial activity to be required for their contacts with P-bodies. However, inactivation of mitochondria leads to a strong decrease of miRNA-mediated RNAi efficiency, and to a lesser extent of siRNA-mediated RNAi. The defect occurs during the assembly of active RISC and is associated with a specific delocalization of endogeneous Ago2 from P-bodies. Our study reveals the possible involvement of RNAi defect in pathologies involving mitochondrial deficiencies.