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Proofreading deficiency in mitochondrial DNA polymerase does not affect total dNTP pools in mouse embryos

Nature Metabolism volume 2, pages 673–675 (2020)Cite this article

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Matters Arising to this article was published on 10 August 2020

The Original Article was published on 07 October 2019

arising from R. H. Hämäläinen et al. Nature Metabolism https://doi.org/10.1038/s42255-019-0120-1 (2019)

Mitochondrial DNA (mtDNA) mutator mice express proofreading-deficient mtDNA polymerase gamma (PolgD257A) and age prematurely1,2, whereas mice with other mitochondrial defects do not show global signs of early ageing. The reason for this discrepancy is not completely understood. Hämäläinen et al.3 recently reported that both induced pluripotent stem cells (iPSCs) and primary embryonic fibroblasts harbouring PolgD257A demonstrate increased mtDNA replication frequency, leading to depletion of the total cellular deoxynucleoside 5′-triphosphate (dNTP) pool. The authors proposed that the decreased availability of cellular dNTPs for nuclear-genome replication leads to compromised nuclear-genome maintenance and premature ageing. Here, we report that total cellular dNTP pools are normal in mtDNA mutator mouse embryos (genotype PolgD257A/D257A), which shows that a living organism exclusively expressing PolgD257A has normal total dNTP pools despite ubiquitous rapid cell division.

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Fig. 1: dNTP pools in E13.5 mouse embryos.

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Authors and Affiliations

  1. Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden

    Sushma Sharma, Phong Tran, Anna Karin Nilsson & Andrei Chabes

  2. Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden

    Camilla Koolmeister & Nils-Göran Larsson

  3. Max Planck Institute for Biology of Ageing - Karolinska Institutet Laboratory, Karolinska Institutet, Stockholm, Sweden

    Camilla Koolmeister & Nils-Göran Larsson

Authors
  1. Sushma Sharma
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  2. Camilla Koolmeister
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  6. Andrei Chabes
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Contributions

C.K. isolated and genotyped Polg mouse embryos and P.T. and A.K.N. isolated and genotyped Samhd1 mouse embryos. S.S. performed the dNTP-pool measurements. S.S., N.-G.L. and A.C. analysed the data. A.C. wrote the manuscript.

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Correspondence to Andrei Chabes.

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Sharma, S., Koolmeister, C., Tran, P. et al. Proofreading deficiency in mitochondrial DNA polymerase does not affect total dNTP pools in mouse embryos. Nat Metab 2, 673–675 (2020). https://doi.org/10.1038/s42255-020-0264-z

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