The mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are specific ER domains that contact the mitochondria and function to facilitate communication between ER and mitochondria. Disruption of contact between the mitochondria and ER is associated with a variety of pathophysiological conditions including neurodegenerative diseases. Considering the many cellular functions of MAMs, we hypothesized that MAMs play an important role in regulating microRNA (miRNA) activity linked to its unique location between mitochondria and ER. Here we present new findings from human and rat brains indicating that the MAMs are subcellular sites enriched for specific miRNAs. We employed subcellular fractionation and TaqMan® RT-qPCR miRNA analysis to quantify miRNA levels in subcellular fractions isolated from male rat brains and six human brain samples. We found that MAMs contain a substantial number of miRNAs and the profile differs significantly from that of cytosolic, mitochondria, or ER. Interestingly, MAMs are particularly enriched in inflammatory-responsive miRNAs, including miR-146a, miR-142-3p, and miR-142-5p in both human and rat brains; miR-223 MAM enrichment was observed only in human brain samples. Further, mitochondrial uncoupling or traumatic brain injury in male rats resulted in the alteration of inflammatory miRNA enrichment in the isolated subcellular fractions. These observations demonstrate that miRNAs are distributed differentially in organelles and may re-distribute between organelles and the cytosol in response to cellular stress and metabolic demands.

线粒体相关内质网 (ER) 膜 (MAM) 是与线粒体接触的特定 ER 结构域，其功能是促进 ER 与线粒体之间的通讯。线粒体和内质网之间接触的破坏与包括神经退行性疾病在内的多种病理生理状况有关。考虑到 MAM 的多种细胞功能，我们假设 MAM 在调节 microRNA (miRNA) 活性方面​​发挥着重要作用，这与其在线粒体和 ER 之间的独特位置有关。在这里，我们提出了来自人类和大鼠大脑的新发现，表明 MAM 是富含特定 miRNA 的亚细胞位点。我们采用亚细胞分级分离和 TaqMan® RT-qPCR miRNA 分析来量化从雄性大鼠大脑和六个人脑样本中分离的亚细胞组分中的 miRNA 水平。我们发现 MAM 含有大量 miRNA，并且其特征与胞质、线粒体或 ER 的特征显着不同。有趣的是，MAM 尤其富含炎症反应性 miRNA，包括人和大鼠大脑中的 miR-146a、miR-142-3p 和 miR-142-5p；仅在人脑样本中观察到 miR-223 MAM 富集。此外，雄性大鼠的线粒体解偶联或创伤性脑损伤导致分离的亚细胞部分中炎症 miRNA 富集的改变。这些观察结果表明，miRNA 在细胞器中的分布存在差异，并且可能响应细胞应激和代谢需求而在细胞器和细胞质之间重新分布。