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

Nature Metabolism volume 2, pages 676–677 (2020)Cite this article

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The Original Article was published on 10 August 2020

replying to S. Sharma et al. Nature Metabolism https://doi.org/10.1038/s42255-020-0264-z (2020)

In their correspondence related to our recent article about the mechanism underlying the progeria phenotype in mitochondrial DNA (mtDNA) mutator mice, Sharma et al.1 raise technical concerns about our methodology for dNTP analysis. These mice have been considered important in vivo evidence for the link between mtDNA mutagenesis and ageing-like symptoms2,3,4. Our evidence suggests that mtDNA mutagenesis is not the sole explanation for progeric features in these mice, and that there is a unifying mechanism for mouse progeroid models based on nuclear-DNA damage. Importantly, Sharma et al. do not challenge this conclusion.

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References

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Author notes

  1. These authors contributed equally: Juan C. Landoni, Kati J. Ahlqvist.

Authors and Affiliations

  1. A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland

    Riikka H. Hämäläinen, Sanna Ryytty & M. Obaidur Rahman

  2. Research Programs Unit, Stem Cells and Metabolism, University of Helsinki, Helsinki, Finland

    Riikka H. Hämäläinen, Juan C. Landoni, Kati J. Ahlqvist, Virginia Brilhante & Anu Suomalainen

  3. Department of Environmental and Biological Sciences, University of Eastern Finland, Joensuu, Finland

    Steffi Goffart

  4. Research Programs Unit, Genome-Scale Biology, University of Helsinki, Helsinki, Finland

    Katherine Icay & Sampsa Hautaniemi

  5. Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden

    Liya Wang

  6. Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Marikki Laiho

  7. University Hospital, Department of Neurology, Helsinki, Finland

    Anu Suomalainen

  8. Neuroscience Center, University of Helsinki, Helsinki, Finland

    Anu Suomalainen

Authors
  1. Riikka H. Hämäläinen
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  10. Liya Wang
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  11. Marikki Laiho
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  12. Anu Suomalainen
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Contributions

R.H.H., J.C.L., K.J.A., S.G., S.R., M.O.R., V.B., K.I., S.H., L.W., M.L. and A.S. wrote the manuscript. L.W. performed experimental work and data analysis

Corresponding authors

Correspondence to Riikka H. Hämäläinen or Anu Suomalainen.

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Hämäläinen, R.H., Landoni, J.C., Ahlqvist, K.J. et al. Reply to: Proofreading deficiency in mitochondrial DNA polymerase does not affect total dNTP pools in mouse embryos. Nat Metab 2, 676–677 (2020). https://doi.org/10.1038/s42255-020-0265-y

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