Coupling of ribosome biogenesis and translation initiation in human mitochondria

Marleen Heinrichs, Anna Franziska Finke, Shintaro Aibara, Angelique Krempler, Angela Boshnakovska, Peter Rehling, Hauke S. Hillen () and Ricarda Richter-Dennerlein ()
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Marleen Heinrichs: University Medical Center Göttingen
Anna Franziska Finke: University Medical Center Göttingen
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
Hauke S. Hillen: University of Göttingen
Ricarda Richter-Dennerlein: University Medical Center Göttingen

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-58827-x

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