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Review
. 2023 Jan 19;24(3):1969.
doi: 10.3390/ijms24031969.

Mitochondrial Transplantation in Mitochondrial Medicine: Current Challenges and Future Perspectives

Marco D'Amato  1 , Francesca Morra  1 , Ivano Di Meo  1 , Valeria Tiranti  1
Affiliations
Review

Mitochondrial Transplantation in Mitochondrial Medicine: Current Challenges and Future Perspectives

Marco D'Amato et al. Int J Mol Sci. .

Abstract

Mitochondrial diseases (MDs) are inherited genetic conditions characterized by pathogenic mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). Current therapies are still far from being fully effective and from covering the broad spectrum of mutations in mtDNA. For example, unlike heteroplasmic conditions, MDs caused by homoplasmic mtDNA mutations do not yet benefit from advances in molecular approaches. An attractive method of providing dysfunctional cells and/or tissues with healthy mitochondria is mitochondrial transplantation. In this review, we discuss what is known about intercellular transfer of mitochondria and the methods used to transfer mitochondria both in vitro and in vivo, and we provide an outlook on future therapeutic applications. Overall, the transfer of healthy mitochondria containing wild-type mtDNA copies could induce a heteroplasmic shift even when homoplasmic mtDNA variants are present, with the aim of attenuating or preventing the progression of pathological clinical phenotypes. In summary, mitochondrial transplantation is a challenging but potentially ground-breaking option for the treatment of various mitochondrial pathologies, although several questions remain to be addressed before its application in mitochondrial medicine.

Keywords: mitochondria; mitochondrial diseases; mitochondrial dysfunction; mitochondrial medicine; mitochondrial transplantation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the treatments for mitochondrial diseases. Illustrated are the current treatment strategies for mitochondrial diseases, which can be classified into pharmacological and metabolic (red) and molecular (blue) approaches.
Figure 2
Figure 2
The mechanisms of intercellular mitochondrial transfer. Under the stimulation of stress conditions, mitochondria can be transported bidirectionally between cell A and B via the TNT structure and mitochondria-containing EVs. The formation of TNT is driven by the actin, and mitochondrial transfer between TNT-linked cells is regulated by Miro1. EV endocytosis is mediated by the NAD+/CD38/cADPR/Ca2+ pathway: Under stress, intracellular NAD+ increases and diffuses to the extracellular environment. CD38 then catalyses NAD+ to produce cADPR, a second messenger that acts on Ryanodine Receptor (RyR) on the Endoplasmic reticulum to induce the release of the intracellular Ca2+. Following the increase of cytoplasmic Ca2+ mediates the activation of exocyst complex, leading to the formation and release of vesicles.
Figure 3
Figure 3
Schematic illustration of mitochondrial transplantation methods in vitro. (A) Coincubation, (B) direct microinjection, (C) cell-penetrating peptide mitochondrial delivery, (D) mitoception, (E) photothermal nanoblade, (F) magnetomitotransfer, (G) Mitopunch, (H) FluidFM, (I) EV mitochondrial delivery.
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References

    1. Rossmann M.P., Dubois S.M., Agarwal S., Zon L.I. Mitochondrial Function in Development and Disease. Dis. Model. Mech. 2021;14:dmm048912. doi: 10.1242/dmm.048912. - DOI - PMC - PubMed
    1. Vinten-Johansen J. Commentary: Mitochondria Are More than Just the Cells’ Powerhouse. J. Thorac. Cardiovasc. Surg. 2020;160:e33–e34. doi: 10.1016/j.jtcvs.2019.07.029. - DOI - PubMed
    1. Giacomello M., Pyakurel A., Glytsou C., Scorrano L. The Cell Biology of Mitochondrial Membrane Dynamics. Nat. Rev. Mol. Cell Biol. 2020;21:204–224. doi: 10.1038/s41580-020-0210-7. - DOI - PubMed
    1. Whitley B.N., Engelhart E.A., Hoppins S. Mitochondrial Dynamics and Their Potential as a Therapeutic Target. Mitochondrion. 2019;49:269–283. doi: 10.1016/j.mito.2019.06.002. - DOI - PMC - PubMed
    1. Roger A.J., Muñoz-Gómez S.A., Kamikawa R. The Origin and Diversification of Mitochondria. Curr. Biol. 2017;27:R1177–R1192. doi: 10.1016/j.cub.2017.09.015. - DOI - PubMed

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