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Coupling of ribosome biogenesis and translation initiation in human mitochondria

Author

Listed:
  • Marleen Heinrichs

    (University Medical Center Göttingen
    University of Göttingen)

  • Anna Franziska Finke

    (University Medical Center Göttingen
    Max Planck Institute for Multidisciplinary Sciences)

  • Shintaro Aibara

    (Max Planck Institute for Multidisciplinary Sciences)

  • Angelique Krempler

    (University Medical Center Göttingen)

  • Angela Boshnakovska

    (University Medical Center Göttingen)

  • Peter Rehling

    (University of Göttingen
    University Medical Center Göttingen
    Max Planck Institute for Multidisciplinary Sciences
    Translational Neuroinflammation and Automated Microscopy)

  • Hauke S. Hillen

    (University of Göttingen
    University Medical Center Göttingen
    Max Planck Institute for Multidisciplinary Sciences
    University of Göttingen)

  • Ricarda Richter-Dennerlein

    (University Medical Center Göttingen
    University of Göttingen
    University of Göttingen)

Abstract

Biogenesis of mitoribosomes requires dedicated chaperones, RNA-modifying enzymes, and GTPases, and defects in mitoribosome assembly lead to severe mitochondriopathies in humans. Here, we characterize late-step assembly states of the small mitoribosomal subunit (mtSSU) by combining genetic perturbation and mutagenesis analysis with biochemical and structural approaches. Isolation of native mtSSU biogenesis intermediates via a FLAG-tagged variant of the GTPase MTG3 reveals three distinct assembly states, which show how factors cooperate to mature the 12S rRNA. In addition, we observe four distinct primed initiation mtSSU states with an incompletely matured rRNA, suggesting that biogenesis and translation initiation are not mutually exclusive processes but can occur simultaneously. Together, these results provide insights into mtSSU biogenesis and suggest a functional coupling between ribosome biogenesis and translation initiation in human mitochondria.

Suggested Citation

  • Marleen Heinrichs & Anna Franziska Finke & Shintaro Aibara & Angelique Krempler & Angela Boshnakovska & Peter Rehling & Hauke S. Hillen & Ricarda Richter-Dennerlein, 2025. "Coupling of ribosome biogenesis and translation initiation in human mitochondria," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58827-x
    DOI: 10.1038/s41467-025-58827-x
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    References listed on IDEAS

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    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. Franziska Nadler & Elena Lavdovskaia & Angelique Krempler & Luis Daniel Cruz-Zaragoza & Sven Dennerlein & Ricarda Richter-Dennerlein, 2022. "Human mtRF1 terminates COX1 translation and its ablation induces mitochondrial ribosome-associated quality control," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
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