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Assisted reproductive technologies to prevent human mitochondrial disease transmission

A Corrigendum to this article was published on 06 July 2018

A Corrigendum to this article was published on 06 February 2018

This article has been updated


Mitochondria are essential cytoplasmic organelles that generate energy (ATP) by oxidative phosphorylation and mediate key cellular processes such as apoptosis. They are maternally inherited and in humans contain a 16,569-base-pair circular genome (mtDNA) encoding 37 genes required for oxidative phosphorylation. Mutations in mtDNA cause a range of pathologies, commonly affecting energy-demanding tissues such as muscle and brain. Because mitochondrial diseases are incurable, attention has focused on limiting the inheritance of pathogenic mtDNA by mitochondrial replacement therapy (MRT). MRT aims to avoid pathogenic mtDNA transmission between generations by maternal spindle transfer, pronuclear transfer or polar body transfer: all involve the transfer of nuclear DNA from an egg or zygote containing defective mitochondria to a corresponding egg or zygote with normal mitochondria. Here we review recent developments in animal and human models of MRT and the underlying biology. These have led to potential clinical applications; we identify challenges to their technical refinement.

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Figure 1: Genetic map of mtDNA showing positions and nomenclature of mutations and population haplogroups.
Figure 2: Migration patterns of mitochondrial haplogroups.
Figure 3: Distribution patterns of mutated mtDNA in oocytes in three families with pathogenic mutations.
Figure 4: Protocols for mitochondrial replacement therapy.

Change history

  • 14 December 2017

    In the version of this article initially published, in Table 2, first column, “m.13095T > C” should have been “m.130bT > C,” where “b” refers to the footnote “Characters hidden to respect confidentiality,” as with the other three from the Newcastle Group. In addition, the footnote “a” for Table 2 should have read “” rather than “Personal communication.” The following acknowledgment was omitted: “The authors thank Rob Taylor, Charlotte Alston, Emma Watson, Sam Byerley, Jane Stewart and Robert McFarland (Wellcome Centre for Mitochondrial Research Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust) for unpublished data included in Table 2.” The errors have been corrected in the HTML and PDF versions of the article.


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A.C.F.P. is grateful for support from the Medical Research Council, UK (grants MR/N000080/1 and MR/N020294/1). The authors thank Rob Taylor, Charlotte Alston, Emma Watson, Sam Byerley, Jane Stewart and Robert McFarland (Wellcome Centre for Mitochondrial Research Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust) for unpublished data included in Table 2.

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Greenfield, A., Braude, P., Flinter, F. et al. Assisted reproductive technologies to prevent human mitochondrial disease transmission. Nat Biotechnol 35, 1059–1068 (2017).

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