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Exonuclease EXD2 in mitochondrial translation

Nature Cell Biology volume 20, pages 120–122 (2018)Cite this article

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Elucidating regulation of mitochondrial mRNA translation will improve our understanding of mitochondrial function during homeostasis and disease. Ribonuclease EXD2 is now shown to be important for mitochondrial translation and oxidative phosphorylation, and its loss enhances ROS production, slows development and extends lifespan in flies.

EXD2 encodes a 3′–5′ exonuclease with predicted homology to the exonuclease domain of the Werner syndrome protein, as well as a HNH-motif usually found in endonucleases. EXD2 was previously identified as necessary for resistance to mitomycin C (MMC), a DNA inter-strand crosslinking reagent2. It was also found that depletion of EXD2 sensitized cells to a number of other DNA-damaging agents, including the Topo1 inhibitor, camptothecin (CPT); the alkylating agent, methyl methanesulfonate (MMS); and the DNA intercalator, phleomycin2,3. The use of proteomics to identify proteins enriched on the stalled replication fork also identified EXD24. Further studies found that EXD2 is important for the repair of DNA double-strand breaks by homologous recombination through its 3′–5′ exonuclease activity, promoting resection (the generation of single-stranded DNA overhangs)3.

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Fig. 1: The exonuclease EXD2 plays an important role in mitochondrial mRNA-encoded translation, organismal ROS production and prolonged lifespan.

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Authors and Affiliations

  1. Department of Chemistry & Biochemistry, University of California San Diego, La Jolla, CA, USA

    Brian M. Zid

  2. Buck Institute for Research on Aging, Novato, CA, USA

    Pankaj Kapahi

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  1. Brian M. Zid
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  2. Pankaj Kapahi
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Correspondence to Brian M. Zid or Pankaj Kapahi.

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Zid, B.M., Kapahi, P. Exonuclease EXD2 in mitochondrial translation. Nat Cell Biol 20, 120–122 (2018). https://doi.org/10.1038/s41556-017-0031-x

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