Genetic Drift Can Compromise Mitochondrial Replacement by Nuclear Transfer in Human Oocytes
Overview
Authors
Affiliations
Replacement of mitochondria through nuclear transfer between oocytes of two different women has emerged recently as a strategy for preventing inheritance of mtDNA diseases. Although experiments in human oocytes have shown effective replacement, the consequences of small amounts of mtDNA carryover have not been studied sufficiently. Using human mitochondrial replacement stem cell lines, we show that, even though the low levels of heteroplasmy introduced into human oocytes by mitochondrial carryover during nuclear transfer often vanish, they can sometimes instead result in mtDNA genotypic drift and reversion to the original genotype. Comparison of cells with identical oocyte-derived nuclear DNA but different mtDNA shows that either mtDNA genotype is compatible with the nucleus and that drift is independent of mitochondrial function. Thus, although functional replacement of the mitochondrial genome is possible, even low levels of heteroplasmy can affect the stability of the mtDNA genotype and compromise the efficacy of mitochondrial replacement.
Discussions on Human Enhancement Meet Science: A Quantitative Analysis.
Zuradzki T, Bystranowski P, Dranseika V Sci Eng Ethics. 2025; 31(1):6.
PMID: 39907843 PMC: 11799069. DOI: 10.1007/s11948-025-00531-6.
Mitochondrial diseases: from molecular mechanisms to therapeutic advances.
Wen H, Deng H, Li B, Chen J, Zhu J, Zhang X Signal Transduct Target Ther. 2025; 10(1):9.
PMID: 39788934 PMC: 11724432. DOI: 10.1038/s41392-024-02044-3.
Mitochondrial DNA variants correlate with a primary open-angle glaucoma subgroup.
Vallbona-Garcia A, Lindsey P, Kamps R, Stassen A, Nguyen N, van Tienen F Front Ophthalmol (Lausanne). 2024; 3:1309836.
PMID: 38983060 PMC: 11182222. DOI: 10.3389/fopht.2023.1309836.
Precision mitochondrial medicine.
Chinnery P Camb Prism Precis Med. 2024; 1():e6.
PMID: 38550943 PMC: 10953752. DOI: 10.1017/pcm.2022.8.
Mitochondrial transfer - a novel promising approach for the treatment of metabolic diseases.
Chen R, Chen J Front Endocrinol (Lausanne). 2024; 14:1346441.
PMID: 38313834 PMC: 10837849. DOI: 10.3389/fendo.2023.1346441.