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Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol

Author

Listed:
  • Lidia Wrobel

    (International Institute of Molecular and Cell Biology)

  • Ulrike Topf

    (International Institute of Molecular and Cell Biology)

  • Piotr Bragoszewski

    (International Institute of Molecular and Cell Biology)

  • Sebastian Wiese

    (Faculty of Biology and BIOSS Centre for Biological Signalling Studies, University of Freiburg
    ZBSA Centre for Biological Systems Analysis, University of Freiburg
    † Present address: Core Unit Mass Spectrometry and Proteomics, Medical Faculty, Ulm University, D-89081 Ulm, Germany.)

  • Malgorzata E. Sztolsztener

    (International Institute of Molecular and Cell Biology)

  • Silke Oeljeklaus

    (Faculty of Biology and BIOSS Centre for Biological Signalling Studies, University of Freiburg)

  • Aksana Varabyova

    (International Institute of Molecular and Cell Biology)

  • Maciej Lirski

    (Institute of Biochemistry and Biophysics Polish Academy of Sciences)

  • Piotr Chroscicki

    (International Institute of Molecular and Cell Biology)

  • Seweryn Mroczek

    (Institute of Biochemistry and Biophysics Polish Academy of Sciences
    Faculty of Biology, University of Warsaw)

  • Elzbieta Januszewicz

    (International Institute of Molecular and Cell Biology)

  • Andrzej Dziembowski

    (Institute of Biochemistry and Biophysics Polish Academy of Sciences
    Faculty of Biology, University of Warsaw)

  • Marta Koblowska

    (Institute of Biochemistry and Biophysics Polish Academy of Sciences
    Laboratory of Systems Biology, Faculty of Biology, University of Warsaw)

  • Bettina Warscheid

    (Faculty of Biology and BIOSS Centre for Biological Signalling Studies, University of Freiburg
    ZBSA Centre for Biological Systems Analysis, University of Freiburg)

  • Agnieszka Chacinska

    (International Institute of Molecular and Cell Biology)

Abstract

Mitochondrial dysfunction and cellular protein homeostasis failure are hallmarks of many diseases and age-associated pathologies; this study shows that the mitochondrial import defect of nuclear-encoded proteins triggers a cellular pathway, termed unfolded protein response activated by mistargeting of proteins (UPRam), that acts to minimize the stress caused by non-imported mitochondrial precursor proteins in order to sustain cellular protein homeostasis and organismal fitness.

Suggested Citation

  • Lidia Wrobel & Ulrike Topf & Piotr Bragoszewski & Sebastian Wiese & Malgorzata E. Sztolsztener & Silke Oeljeklaus & Aksana Varabyova & Maciej Lirski & Piotr Chroscicki & Seweryn Mroczek & Elzbieta Jan, 2015. "Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol," Nature, Nature, vol. 524(7566), pages 485-488, August.
    • Handle: RePEc:nat:nature:v:524:y:2015:i:7566:d:10.1038_nature14951
    DOI: 10.1038/nature14951
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    Citations

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    Cited by:

    1. Hope I. Needs & Emily Glover & Gonçalo C. Pereira & Alina Witt & Wolfgang Hübner & Mark P. Dodding & Jeremy M. Henley & Ian Collinson, 2024. "Rescue of mitochondrial import failure by intercellular organellar transfer," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Evelyn Fessler & Luisa Krumwiede & Lucas T. Jae, 2022. "DELE1 tracks perturbed protein import and processing in human mitochondria," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Eirini Lionaki & Ilias Gkikas & Ioanna Daskalaki & Maria-Konstantina Ioannidi & Maria I. Klapa & Nektarios Tavernarakis, 2022. "Mitochondrial protein import determines lifespan through metabolic reprogramming and de novo serine biosynthesis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. 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.
    5. Minji Kim & Remigiusz A. Serwa & Lukasz Samluk & Ida Suppanz & Agata Kodroń & Tomasz M. Stępkowski & Praveenraj Elancheliyan & Biniyam Tsegaye & Silke Oeljeklaus & Michal Wasilewski & Bettina Warschei, 2023. "Immunoproteasome-specific subunit PSMB9 induction is required to regulate cellular proteostasis upon mitochondrial dysfunction," Nature Communications, Nature, vol. 14(1), pages 1-23, December.

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