IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-58827-x.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-58827-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-58827-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    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. 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.
    5. Nathan J. Harper & Chloe Burnside & Sebastian Klinge, 2023. "Principles of mitoribosomal small subunit assembly in eukaryotes," Nature, Nature, vol. 614(7946), pages 175-181, February.
    6. Thu Giang Nguyen & Christina Ritter & Eva Kummer, 2023. "Structural insights into the role of GTPBP10 in the RNA maturation of the mitoribosome," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    7. 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.
    8. 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.
    9. 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.
    10. Eva Kummer & Marc Leibundgut & Oliver Rackham & Richard G. Lee & Daniel Boehringer & Aleksandra Filipovska & Nenad Ban, 2018. "Unique features of mammalian mitochondrial translation initiation revealed by cryo-EM," Nature, Nature, vol. 560(7717), pages 263-267, August.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. 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.
    2. Vivek Singh & Yuzuru Itoh & Samuel Del’Olio & Asem Hassan & Andreas Naschberger & Rasmus Kock Flygaard & Yuko Nobe & Keiichi Izumikawa & Shintaro Aibara & Juni Andréll & Paul C. Whitford & Antoni Barr, 2024. "Mitoribosome structure with cofactors and modifications reveals mechanism of ligand binding and interactions with L1 stalk," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    3. Thu Giang Nguyen & Christina Ritter & Eva Kummer, 2023. "Structural insights into the role of GTPBP10 in the RNA maturation of the mitoribosome," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Bo Qin & Simon M. Lauer & Annika Balke & Carlos H. Vieira-Vieira & Jörg Bürger & Thorsten Mielke & Matthias Selbach & Patrick Scheerer & Christian M. T. Spahn & Rainer Nikolay, 2023. "Cryo-EM captures early ribosome assembly in action," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    5. 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.
    6. 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.
    7. Lisa Kofler & Lorenz Grundmann & Magdalena Gerhalter & Michael Prattes & Juliane Merl-Pham & Gertrude Zisser & Irina Grishkovskaya & Victor-Valentin Hodirnau & Martin Vareka & Rolf Breinbauer & Stefan, 2024. "The novel ribosome biogenesis inhibitor usnic acid blocks nucleolar pre-60S maturation," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    8. Gabrielle Bourgeois & Pierre-Damien Coureux & Christine Lazennec-Schurdevin & Clément Madru & Thomas Gaillard & Magalie Duchateau & Julia Chamot-Rooke & Sophie Bourcier & Yves Mechulam & Emmanuelle Sc, 2025. "Structures of Saccharolobus solfataricus initiation complexes with leaderless mRNAs highlight archaeal features and eukaryotic proximity," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    9. Annika Krüger & Cristina Remes & Dmitrii Igorevich Shiriaev & Yong Liu & Henrik Spåhr & Rolf Wibom & Ilian Atanassov & Minh Duc Nguyen & Barry S. Cooperman & Joanna Rorbach, 2023. "Human mitochondria require mtRF1 for translation termination at non-canonical stop codons," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    10. Xiang Li & Mengjiao Wang & Timo Denk & Robert Buschauer & Yi Li & Roland Beckmann & Jingdong Cheng, 2024. "Structural basis for differential inhibition of eukaryotic ribosomes by tigecycline," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58827-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.