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Miro1 improves the exogenous engraftment efficiency and therapeutic potential of mitochondria transfer using Wharton's jelly mesenchymal stem cells.
- Source :
-
Mitochondrion [Mitochondrion] 2024 May; Vol. 76, pp. 101856. Date of Electronic Publication: 2024 Feb 24. - Publication Year :
- 2024
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Abstract
- 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.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Published by Elsevier B.V.)
- Subjects :
- Humans
Apoptosis
Cell Proliferation
Cells, Cultured
DNA, Mitochondrial genetics
DNA, Mitochondrial metabolism
Fibroblasts metabolism
Membrane Potential, Mitochondrial
Mesenchymal Stem Cell Transplantation methods
Mitochondrial Proteins genetics
Mitochondrial Proteins metabolism
Reactive Oxygen Species metabolism
Mesenchymal Stem Cells metabolism
Mitochondria metabolism
rho GTP-Binding Proteins metabolism
rho GTP-Binding Proteins genetics
Wharton Jelly cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-8278
- Volume :
- 76
- Database :
- MEDLINE
- Journal :
- Mitochondrion
- Publication Type :
- Academic Journal
- Accession number :
- 38408618
- Full Text :
- https://doi.org/10.1016/j.mito.2024.101856