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Mistargeting of aggregation prone mitochondrial proteins activates a nucleus-mediated posttranscriptional quality control pathway in trypanosomes

Author

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  • Caroline E. Dewar

    (University of Bern, Freiestrasse 3)

  • Silke Oeljeklaus

    (Theodor Boveri-Institute, University of Würzburg
    University of Freiburg)

  • Jan Mani

    (University of Bern, Freiestrasse 3)

  • Wignand W. D. Mühlhäuser

    (University of Freiburg)

  • Corinne Känel

    (University of Bern, Freiestrasse 3)

  • Johannes Zimmermann

    (Theodor Boveri-Institute, University of Würzburg)

  • Torsten Ochsenreiter

    (University of Bern, Baltzerstrasse 4)

  • Bettina Warscheid

    (Theodor Boveri-Institute, University of Würzburg
    University of Freiburg
    University of Freiburg)

  • André Schneider

    (University of Bern, Freiestrasse 3)

Abstract

Mitochondrial protein import in the parasitic protozoan Trypanosoma brucei is mediated by the atypical outer membrane translocase, ATOM. It consists of seven subunits including ATOM69, the import receptor for hydrophobic proteins. Ablation of ATOM69, but not of any other subunit, triggers a unique quality control pathway resulting in the proteasomal degradation of non-imported mitochondrial proteins. The process requires a protein of unknown function, an E3 ubiquitin ligase and the ubiquitin-like protein (TbUbL1), which all are recruited to the mitochondrion upon ATOM69 depletion. TbUbL1 is a nuclear protein, a fraction of which is released to the cytosol upon triggering of the pathway. Nuclear release is essential as cytosolic TbUbL1 can bind mislocalised mitochondrial proteins and likely transfers them to the proteasome. Mitochondrial quality control has previously been studied in yeast and metazoans. Finding such a pathway in the highly diverged trypanosomes suggests such pathways are an obligate feature of all eukaryotes.

Suggested Citation

  • Caroline E. Dewar & Silke Oeljeklaus & Jan Mani & Wignand W. D. Mühlhäuser & Corinne Känel & Johannes Zimmermann & Torsten Ochsenreiter & Bettina Warscheid & André Schneider, 2022. "Mistargeting of aggregation prone mitochondrial proteins activates a nucleus-mediated posttranscriptional quality control pathway in trypanosomes," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30748-z
    DOI: 10.1038/s41467-022-30748-z
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    References listed on IDEAS

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    1. Christian D. Peikert & Jan Mani & Marcel Morgenstern & Sandro Käser & Bettina Knapp & Christoph Wenger & Anke Harsman & Silke Oeljeklaus & André Schneider & Bettina Warscheid, 2017. "Charting organellar importomes by quantitative mass spectrometry," Nature Communications, Nature, vol. 8(1), pages 1-14, August.
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