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Safeguarding mitochondrial genomes in higher eukaryotes

Nature Structural & Molecular Biology volume 27, pages 687–695 (2020)Cite this article

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Abstract

Mitochondria respond to DNA damage and preserve their own genetic material in a manner distinct from that of the nucleus but that requires organized mito–nuclear communication. Failure to resolve mtDNA breaks leads to mitochondrial dysfunction and affects host cells and tissues. Here, we review the pathways that safeguard mitochondrial genomes and examine the insights gained from studies of cellular and tissue-wide responses to mtDNA damage and mito–nuclear genome incompatibility.

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Fig. 1: Overview of mitochondria, mtDNA and nucleoids.
Fig. 2: Mitochondrial DNA dynamics in response to DSBs.
Fig. 3: Innate immunity as a form of retrograde signaling upon mtDNA dysfunction.

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Acknowledgements

We thank Michael J Smith, Samuel Trembley-Belzille, and Toby Lieber for commenting on the manuscript. Mitochondria-related work in the Sfeir lab is supported by funds from the David and Lucille Packard Foundation, a Mallinckrodt Scholar award and the Pew-Innovation award.

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  1. Skirball Institute of Biomolecular Medicine, Cell Biology Department, NYU Grossman School of Medicine, New York, NY, USA

    Yi Fu, Marco Tigano & Agnel Sfeir

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  1. Yi Fu
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Correspondence to Agnel Sfeir.

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Agnel Sfeir is a cofounder, consultant and shareholder in Repare Therapeutics.

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Fu, Y., Tigano, M. & Sfeir, A. Safeguarding mitochondrial genomes in higher eukaryotes. Nat Struct Mol Biol 27, 687–695 (2020). https://doi.org/10.1038/s41594-020-0474-9

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