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Reversion after replacement of mitochondrial DNA

Nature volume 574, pages E8–E11 (2019)Cite this article

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Matters Arising to this article was published on 16 October 2019

The Original Article was published on 30 November 2016

arising from: E. Kang et al. Nature https://doi.org/10.1038/nature20592 (2016).

The risk of transmitting deleterious mutations in mitochondrial DNA (mtDNA) from mother to child may be reduced by mitochondrial replacement, which involves transplanting the nuclear DNA from the egg of a woman containing such a mutation into an enucleated egg from an unaffected donor1. Although embryonic stem cell lines derived from mitochondrial replacement embryos can revert to the mitochondrial genome of the nuclear donor1, a study that involved eggs from women who carry pathogenic mutations reported that mutant mtDNA was efficiently eliminated and did not re-emerge in embryonic stem cell lines2. Contrary to this, we find that two embryonic stem cell lines derived by Kang et al.2 exhibited reversion to a pathogenic variant, which was present in the mitochondrial genome of a nuclear donor assigned to the control group. Although the clinical relevance is unclear, reversion in embryonic stem cell lines remains a consideration for therapeutic applications of mitochondrial replacement, and accurate reporting of the research that underpins these applications is therefore essential.

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Fig. 1: Reversion to a pathogenic mutation in mtDNA, in ES cell lines derived from mitochondrial replacement embryos.
Fig. 2: Effect of CSBII haplotypes on reversion in ES cell lines after mitochondrial replacement.

Data availability

Previously unpublished4 mtDNA sequence data from ES cell lines are available online (https://doi.org/10.5281/zenodo.3349761). Additional previously published data are available from the respective publications2,3. Further supporting sequence data from ref. 3 were provided to us by one of the authors (D. Egli).

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Acknowledgements

Work in the laboratory of G.H. and M.H. is funded by Wellcome (203105/Z/16/Z). G.H. is a Newcastle University Research Fellow and receives funding from the Michael J. Fox Foundation (ID: 15643).

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Authors and Affiliations

  1. Wellcome Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK

    Gavin Hudson, Yuko Takeda & Mary Herbert

  2. Newcastle Fertility Centre, Newcastle upon Tyne, UK

    Mary Herbert

Authors
  1. Gavin Hudson
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  2. Yuko Takeda
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  3. Mary Herbert
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Contributions

G.H., Y.T. and M.H. performed the analysis. G.H. and M.H. wrote the manuscript with input from Y.T.

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Correspondence to Gavin Hudson or Mary Herbert.

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Extended data figures and tables

Extended Data Table 1 mtDNA CSBII haplotypes of nuclear and mitochondrial donors
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Hudson, G., Takeda, Y. & Herbert, M. Reversion after replacement of mitochondrial DNA. Nature 574, E8–E11 (2019). https://doi.org/10.1038/s41586-019-1623-3

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