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GTPBP8 plays a role in mitoribosome formation in human mitochondria

Author

Listed:
  • Miriam Cipullo

    (Karolinska Institutet)

  • Genís Valentín Gesé

    (Karolinska Institutet)

  • Shreekara Gopalakrishna

    (Karolinska Institutet)

  • Annika Krueger

    (Karolinska Institutet)

  • Vivian Lobo

    (University of Gothenburg
    University of Gothenburg)

  • Maria A. Pirozhkova

    (Tel Aviv University)

  • James Marks

    (National Institutes of Health)

  • Petra Páleníková

    (University of Cambridge)

  • Dmitrii Shiriaev

    (Karolinska Institutet)

  • Yong Liu

    (Karolinska Institutet)

  • Jelena Misic

    (Karolinska Institutet)

  • Yu Cai

    (Karolinska Institutet)

  • Minh Duc Nguyen

    (Karolinska Institutet)

  • Abubakar Abdelbagi

    (Karolinska Institutet)

  • Xinping Li

    (Max-Planck-Institute for Biology of Ageing)

  • Michal Minczuk

    (University of Cambridge)

  • Markus Hafner

    (National Institutes of Health)

  • Daniel Benhalevy

    (Tel Aviv University)

  • Aishe A. Sarshad

    (University of Gothenburg
    University of Gothenburg)

  • Ilian Atanassov

    (Max-Planck-Institute for Biology of Ageing)

  • B. Martin Hällberg

    (Karolinska Institutet)

  • Joanna Rorbach

    (Karolinska Institutet)

Abstract

Mitochondrial gene expression relies on mitoribosomes to translate mitochondrial mRNAs. The biogenesis of mitoribosomes is an intricate process involving multiple assembly factors. Among these factors, GTP-binding proteins (GTPBPs) play important roles. In bacterial systems, numerous GTPBPs are required for ribosome subunit maturation, with EngB being a GTPBP involved in the ribosomal large subunit assembly. In this study, we focus on exploring the function of GTPBP8, the human homolog of EngB. We find that ablation of GTPBP8 leads to the inhibition of mitochondrial translation, resulting in significant impairment of oxidative phosphorylation. Structural analysis of mitoribosomes from GTPBP8 knock-out cells shows the accumulation of mitoribosomal large subunit assembly intermediates that are incapable of forming functional monosomes. Furthermore, fPAR-CLIP analysis reveals that GTPBP8 is an RNA-binding protein that interacts specifically with the mitochondrial ribosome large subunit 16 S rRNA. Our study highlights the role of GTPBP8 as a component of the mitochondrial gene expression machinery involved in mitochondrial large subunit maturation.

Suggested Citation

  • Miriam Cipullo & Genís Valentín Gesé & Shreekara Gopalakrishna & Annika Krueger & Vivian Lobo & Maria A. Pirozhkova & James Marks & Petra Páleníková & Dmitrii Shiriaev & Yong Liu & Jelena Misic & Yu C, 2024. "GTPBP8 plays a role in mitoribosome formation in human mitochondria," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50011-x
    DOI: 10.1038/s41467-024-50011-x
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    References listed on IDEAS

    as
    1. Yuzuru Itoh & Anas Khawaja & Ivan Laptev & Miriam Cipullo & Ilian Atanassov & Petr Sergiev & Joanna Rorbach & Alexey Amunts, 2022. "Mechanism of mitoribosomal small subunit biogenesis and preinitiation," Nature, Nature, vol. 606(7914), pages 603-608, June.
    2. Pedro Rebelo-Guiomar & Simone Pellegrino & Kyle C. Dent & Aldema Sas-Chen & Leonor Miller-Fleming & Caterina Garone & Lindsey Van Haute & Jack F. Rogan & Adam Dinan & Andrew E. Firth & Byron Andrews &, 2022. "A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Miriam Cipullo & Genís Valentín Gesé & Anas Khawaja & B. Martin Hällberg & Joanna Rorbach, 2021. "Structural basis for late maturation steps of the human mitoribosomal large subunit," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    4. Jingdong Cheng & Otto Berninghausen & Roland Beckmann, 2021. "A distinct assembly pathway of the human 39S late pre-mitoribosome," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    5. Hauke S. Hillen & Elena Lavdovskaia & Franziska Nadler & Elisa Hanitsch & Andreas Linden & Katherine E. Bohnsack & Henning Urlaub & Ricarda Richter-Dennerlein, 2021. "Structural basis of GTPase-mediated mitochondrial ribosome biogenesis and recycling," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    6. Anas Khawaja & Yuzuru Itoh & Cristina Remes & Henrik Spåhr & Olessya Yukhnovets & Henning Höfig & Alexey Amunts & Joanna Rorbach, 2020. "Distinct pre-initiation steps in human mitochondrial translation," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
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