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• Miro1 over-expression of WJMSCs enhanced intercellular communications and promoted cell proliferation in mitochondria-defective fibroblasts. • Miro1 over-expressed WJMSCs improved mitochondrial membrane potential and cell proliferation rates in mitochondria-defective fibroblasts. • Miro1 over-expressed WJMSCs decreased rotenone-induced apoptosis in mitochondria-defective fibroblasts. • Miro1 over-expressed WJMSCs reduced ROS production and helped restore bioenergetics in mitochondria-defective fibroblasts. • The potential effectiveness of a Miro1-targeted WJMSC-based therapy for restoring mitochondrial function is promising, thereby offering a novel therapeutic approach for MELAS and other mitochondria-related diseases. 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. [ABSTRACT FROM AUTHOR]