Mitochondria are important for maintaining cellular energy metabolism and regulating cellular senescence. Mitochondrial DNA (mtDNA) encodes subunits of the OXPHOS complexes which are essential for cellular respiration and energy production. Meanwhile, mtDNA variants have been associated with the pathogenesis of neurodegenerative diseases, including MELAS, for which no effective treatment has been developed. To alleviate the pathological conditions involved in mitochondrial disorders, mitochondria transfer therapy has shown promise. Wharton's jelly mesenchymal stem cells (WJMSCs) have been identified as suitable mitochondria donors for mitochondria-defective cells, wherein mitochondrial functions can be rescued. Miro1 participates in mitochondria trafficking by anchoring mitochondria to microtubules. In this study, we identified Miro1 over-expression as a factor that could help to enhance the efficiency of mitochondrial delivery. More specifically, we reveal that Miro1 over-expressed WJMSCs significantly improved intercellular communications, cell proliferation rates, and mitochondrial membrane potential, while restoring mitochondrial bioenergetics in mitochondria-defective fibroblasts. Furthermore, Miro1 over-expressed WJMSCs decreased rates of induced apoptosis and ROS production in MELAS fibroblasts; although, Miro1 over-expression did not rescue mtDNA mutation ratios nor mitochondrial biogenesis. This study presents a potentially novel therapeutic strategy for treating mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), and other diseases associated with dysfunctional mitochondria, while the pathophysiological relevance of our results should be further verified by animal models and clinical studies.

中文翻译：

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Miro1 提高了沃顿胶体间充质干细胞线粒体移植的外源植入效率和治疗潜力

线粒体对于维持细胞能量代谢和调节细胞衰老很重要。线粒体 DNA (mtDNA) 编码 OXPHOS 复合物的亚基，该复合物对于细胞呼吸和能量产生至关重要。与此同时，线粒体DNA变异与神经退行性疾病（包括MELAS）的发病机制有关，但目前尚未开发出有效的治疗方法。为了缓解与线粒体疾病有关的病理状况，线粒体转移疗法已显示出希望。沃顿商学院的果冻间充质干细胞（WJMSC）已被确定为线粒体缺陷细胞的合适线粒体供体，其中线粒体功能可以得到挽救。Miro1 通过将线粒体锚定到微管来参与线粒体运输。在这项研究中，我们发现 Miro1 过度表达是有助于提高线粒体递送效率的一个因素。更具体地说，我们发现 Miro1 过表达的 WJMSC 显着改善了细胞间通讯、细胞增殖率和线粒体膜电位，同时恢复了线粒体缺陷的成纤维细胞的线粒体生物能。此外，Miro1 过表达 WJMSC 会降低 MELAS 成纤维细胞诱导细胞凋亡和 ROS 产生的速率。然而，Miro1 过度表达并不能挽救 mtDNA 突变率，也不能挽救线粒体生物发生。这项研究提出了一种潜在的新颖治疗策略，用于治疗线粒体脑肌病、乳酸性酸中毒和中风样发作（MELAS）以及与线粒体功能障碍相关的其他疾病，而我们结果的病理生理学相关性应通过动物模型和临床研究进一步验证。