Miro1 regulates intercellular mitochondrial transport & enhances mesenchymal stem cell rescue efficacy
Open accessAbstract
There is emerging evidence that stem cells can rejuvenate damaged cells by mitochondrial transfer. Earlier studies show that epithelial mitochondrial dysfunction is critical in asthma pathogenesis. Here we show for the first time that Miro1, a mitochondrial Rho-GTPase, regulates intercellular mitochondrial movement from mesenchymal stem cells (MSC) to epithelial cells (EC). We demonstrate that overexpression of Miro1 in MSC (MSCmiro(Hi)) leads to enhanced mitochondrial transfer and rescue of epithelial injury, while Miro1 knockdown (MSCmiro(Lo)) leads to loss of efficacy. Treatment with MSCmiro(Hi) was associated with greater therapeutic efficacy, when compared to control MSC, in mouse models of rotenone (Rot) induced airway injury and allergic airway inflammation (AAI). Notably, airway hyperresponsiveness and remodeling were reversed by MSCmiro(Hi) in three separate allergen-induced asthma models. In a human in vitro system, MSCmiro(Hi) reversed mitochondrial dysfunction in bronchial epithelial cells treated with pro-inflammatory supernatant of IL-13-induced macrophages. Anti-inflammatory MSC products like NO, TGF-β, IL-10 and PGE2, were unchanged by Miro1 overexpression, excluding non-specific paracrine effects. In summary, Miro1 overexpression leads to increased stem cell repair.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Miro1 is a calcium-sensitive adaptor protein that attaches mitochondria to the KIF5 motor protein and other accessory proteins like Miro2, TRAK1, TRAK2, and Myo19, thus aiding mitochondrial movement along microtubules.
“Miro1 is a calcium-sensitive adaptor protein that attaches the Mt to the KIF5 motor protein and other accessory proteins like Miro2, TRAK1, TRAK2, and Myo19, thus aiding Mt movement along microtubules [392, 393].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [393]
Genetic modification of key molecular mediators such as Miro1 and CX43 represents a direct and well-supported strategy to optimize the mitochondrial transfer efficiency of MSCs.
“Genetic modification of key molecular mediators responsible for triggering and regulating MT, such as mitochondrial Rho-GTPase 1 (Miro1) and connexin 43 (CX43), represents a direct and well-supported strategy to optimize the MT efficiency of MSCs [392–394].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [393]
Miro overexpression boosted the mitochondrial transfer capacity and therapeutic efficacy of MSCs in animal models of asthma, while its knockdown diminished these effects.
“Ahmad et al. demonstrated that Miro overexpression boosted the MT capacity and therapeutic efficacy of MSCs in animal models of asthma, while its knockdown diminished these effects [393].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [393]
Cites
Mitochondrial Fission, Fusion, and Stress
Youle, R. J., & van der Bliek, A. M. (2012) · Science · doi:10.1126/science.1219855 · Cited by 3,674 · see citing works
During autophagy mitochondria elongate, are spared from degradation and sustain cell viability
Gomes, L. C., Benedetto, G. D., & Scorrano, L. (2011) · Nature Cell Biology · doi:10.1038/ncb2220 · Cited by 1,735 · see citing works
Islam, M. N., Das, S. R., Emin, M. T., Wei, M., Sun, L., Westphalen, K., Rowlands, D. J., Quadri, S. K., Bhattacharya, S., & Bhattacharya, J. (2012) · Nature Medicine · doi:10.1038/nm.2736 · Cited by 1,585 · see citing works
M-Sec promotes membrane nanotube formation by interacting with Ral and the exocyst complex
Hase, K., Kimura, S., Takatsu, H., Ohmae, M., Kawano, S., Kitamura, H., Ito, M., Watarai, H., Hazelett, C. C., Yeaman, C., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1990 · Cited by 402 · see citing works
Chang, K. T., Niescier, R. F., & Min, K.-T. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1106862108 · Cited by 153 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mitochondria Know No Boundaries: Mechanisms and Functions of Intercellular Mitochondrial Transfer
Torralba, D., Baixauli, F., & Sánchez-Madrid, F. (2016) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2016.00107 · Cited by 440 · see citing works
Intercellular mitochondrial transfer as a means of tissue revitalization
Liu, D., Gao, Y., Liu, J., Huang, Y., Yin, J., Feng, Y., Shi, L., Meloni, B. P., Zhang, C., Zheng, M., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00440-z · Cited by 403 · see citing works
Scheiblich, H., Dansokho, C., Mercan, D., Schmidt, S. V., Bousset, L., Wischhof, L., Eikens, F., Odainic, A., Spitzer, J., Griep, A., et al. (2021) · Cell · doi:10.1016/j.cell.2021.09.007 · Cited by 360 · see citing works
Ahmad, T., Sundar, I. K., Lerner, C. A., Gerloff, J., Tormos, A. M., Yao, H., & Rahman, I. (2015) · The FASEB Journal · doi:10.1096/fj.14-268276 · Cited by 264 · see citing works
Self-citationNeural stem cells traffic functional mitochondria via extracellular vesicles
Peruzzotti-Jametti, L., Bernstock, J. D., Willis, C. M., Manferrari, G., Rogall, R., Fernandez-Vizarra, E., Williamson, J. C., Braga, A., van den Bosch, A., Leonardi, T., et al. (2021) · PLOS Biology · doi:10.1371/journal.pbio.3001166 · Cited by 263 · see citing works
Court, A. C., Le‐Gatt, A., Luz‐Crawford, P., Parra, E., Aliaga‐Tobar, V., Bátiz, L. F., Contreras, R. A., Ortúzar, M. I., Kurte, M., Elizondo‐Vega, R., et al. (2020) · The EMBO Reports · doi:10.15252/embr.201948052 · Cited by 259 · see citing works
Targeting vascular and leukocyte communication in angiogenesis, inflammation and fibrosis
Kreuger, J., & Phillipson, M. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.2 · Cited by 160 · see citing works
Chen, K., Dai, H., Yuan, J., Chen, J., Lin, L., Zhang, W., Wang, L., Zhang, J., Li, K., & He, Y. (2018) · Cell Death & Disease · doi:10.1038/s41419-017-0127-z · Cited by 150 · see citing works
Artificial Mitochondria Transfer: Current Challenges, Advances, and Future Applications
Caicedo, A., Aponte, P. M., Cabrera, F., Hidalgo, C., & Khoury, M. (2017) · Stem Cells International · doi:10.1155/2017/7610414 · Cited by 150 · see citing works
Chou, S. H.-Y., Lan, J., Esposito, E., Ning, M., Balaj, L., Ji, X., Lo, E. H., & Hayakawa, K. (2017) · Stroke · doi:10.1161/strokeaha.117.017758 · Cited by 134 · see citing works
Golan, K., Singh, A. K., Kollet, O., Bertagna, M., Althoff, M. J., Khatib-Massalha, E., Petrovich-Kopitman, E., Wellendorf, A. M., Massalha, H., Levin-Zaidman, S., et al. (2020) · Blood · doi:10.1182/blood.2020005399 · Cited by 99 · see citing works
Intercellular mitochondrial transfer: bioenergetic crosstalk between cells
Sinha, P., Islam, M. N., Bhattacharya, S., & Bhattacharya, J. (2016) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2016.05.002 · Cited by 91 · see citing works
Bi, Y., Guo, X., Zhang, M., Zhu, K., Shi, C., Fan, B., Wu, Y., Yang, Z., & Ji, G. (2021) · Stem Cell Research & Therapy · doi:10.1186/s13287-021-02663-5 · Cited by 82 · see citing works
Jansens, R. J. J., Van den Broeck, W., De Pelsmaeker, S., Lamote, J. A. S., Van Waesberghe, C., Couck, L., & Favoreel, H. W. (2017) · Journal of Virology · doi:10.1128/jvi.00749-17 · Cited by 71 · see citing works
Faizan, M. I., Chaudhuri, R., Sagar, S., Albogami, S., Chaudhary, N., Azmi, I., Akhtar, A., Ali, S. M., Kumar, R., Iqbal, J., et al. (2022) · Cells · doi:10.3390/cells11192969 · Cited by 61 · see citing works
Self-citationTherapeutic Effects of Mesenchymal Stromal Cells Require Mitochondrial Transfer and Quality Control
Mukkala, A. N., Jerkic, M., Khan, Z., Szaszi, K., Kapus, A., & Rotstein, O. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242115788 · Cited by 45 · see citing works
Age-related Changes in the Energy of Human Mesenchymal Stem Cells
Barilani, M., Lovejoy, C., Piras, R., Abramov, A. Y., Lazzari, L., & Angelova, P. R. (2022) · Journal of Cellular Physiology · doi:10.1002/jcp.30638 · Cited by 31 · see citing works
Akhtar, A., Shakir, M., Ansari, M. S., Divya, Faizan, M. I., Chauhan, V., Singh, A., Alam, R., Azmi, I., Sharma, S., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102021 · Cited by 21 · see citing works
Self-citationPan, X., Gao, T., & Wang, B. (2025) · Cell & Bioscience · doi:10.1186/s13578-025-01520-9 · Cited by 2 · see citing works
“Miro1 is a calcium-sensitive adaptor protein that attaches the Mt to the KIF5 motor protein and other accessory proteins like Miro2, TRAK1, TRAK2, and Myo19, thus aiding Mt movement along microtubules [392, 393].”
- Authors
- Ahmad, T., Mukherjee, S., Pattnaik, B., Kumar, M., Singh, S., Kumar, M., Rehman, R., Tiwari, B. K., Jha, K. A., Barhanpurkar, A. P., Wani, M. R., Roy, S. S., Mabalirajan, U., Ghosh, B., & Agrawal, A.
- Affiliations
- Institute of Genomics and Integrative Biology (IN)
- All India Institute of Medical Sciences (IN)
- National Centre for Cell Science (IN)
- Corresponding author
- Agrawal, Anurag
- ORCID
- Venue
- The EMBO Journal
- Published
- 2014-01-15
- Volume
- 33
- Issue
- 9
- Pages
- 994-1010
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC4193933
- OpenAlex
- W2168750058
- Cited by
- 542
- References
- 5
- Citations by year
- 2026: 64 · 2025: 32 · 2024: 45 · 2023: 36 · 2022: 42 · 2021: 74 · 2020: 60 · 2019: 38 · 2018: 36 · 2017: 40 · 2016: 37 · 2015: 24 · 2014: 14
- FWCI
- 19.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- MLP (5502)
- BSC (0403)
- Council of Scientific and Industrial Research
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Keywords
- Miro1, intercellular mitochondrial transfer, mesenchymal stem cells, asthma, allergic airway inflammation, airway injury, rotenone, airway hyperresponsiveness, airway remodeling, bronchial epithelial cells, IL-13, macrophages, stem cell therapy
- MeSH terms
- Animals, Biological Transport, Cells, Cultured, Humans, Lung, Mice, Inbred BALB C, Mice, Transgenic, Mitochondria, Genetic Therapy, Treatment Outcome, rho GTP-Binding Proteins, NIH 3T3 Cells, Nanotubes, Mesenchymal Stem Cell Transplantation, Mice, Lung Injury, Mesenchymal Stem Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
