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Mitochondrial Transplantation in Mitochondrial Medicine: Current Challenges and Future Perspectives

Journal

Publisher

MDPI
DOI: 10.3390/ijms24031969

Keywords

mitochondria; mitochondrial diseases; mitochondrial medicine; mitochondrial dysfunction; mitochondrial transplantation

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Mitochondrial diseases are genetic conditions caused by mutations in nuclear or mitochondrial DNA. Existing therapies are insufficient for treating the wide range of mtDNA mutations. Mitochondrial transplantation offers a potential solution by transferring healthy mitochondria to dysfunctional cells or tissues. This review explores the mechanisms and methods of intercellular mitochondrial transfer and discusses its potential therapeutic applications. Mitochondrial transplantation could induce a shift in heteroplasmy and potentially attenuate or prevent pathological phenotypes. However, further research is needed before its widespread use in mitochondrial medicine.
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.

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