bims-tricox 2025-04-20 papers

Issue of 2025–04–20
three papers selected by
Yash Verma, University of Zurich

Trends Biochem Sci. 2025 Apr 11. pii: S0968-0004(25)00056-8. [Epub ahead of print]

Emerging mechanisms of human mitochondrial translation regulation.

Michele Brischigliaro, Ahram Ahn, Seungwoo Hong, Flavia Fontanesi, Antoni Barrientos.

Mitochondrial translation regulation enables precise control over the synthesis of hydrophobic proteins encoded by the organellar genome, orchestrating their membrane insertion, accumulation, and assembly into oxidative phosphorylation (OXPHOS) complexes. Recent research highlights regulation across all translation stages (initiation, elongation, termination, and recycling) through a complex interplay of mRNA structures, specialized translation factors, and unique regulatory mechanisms that adjust protein levels for stoichiometric assembly. Key discoveries include mRNA-programmed ribosomal pausing, frameshifting, and termination-dependent re-initiation, which fine-tune protein synthesis and promote translation of overlapping open reading frames (ORFs) in bicistronic transcripts. In this review, we examine these advances, which are significantly enhancing our understanding of mitochondrial gene expression.

Keywords: RNA folding; mitochondrial translation; programmed ribosomal frameshifting; ribosome stalling; termination-reinitiation

DOI: https://doi.org/10.1016/j.tibs.2025.03.007

Nat Commun. 2025 Apr 17. 16(1): 3641

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, Ricarda Richter-Dennerlein.

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.

DOI: https://doi.org/10.1038/s41467-025-58827-x

Trends Biochem Sci. 2025 Apr 15. pii: S0968-0004(25)00060-X. [Epub ahead of print]

Lipids: emerging actors in mitochondrial protein import.

Mayra A Borrero-Landazabal, Vanessa Linke, Agnieszka Chacinska.

Lipids are emerging as functional players in mitochondrial protein import beyond constituting membranes. Cryo-electron microscopy structures of protein translocases such as translocase of the outer membrane (TOM) and insertases such as translocase of the inner membrane (TIM22) link lipids to protein import by suggesting structural and functional roles for lipids in protein translocation and insertion, and for protein insertases in lipid scrambling.

Keywords: membrane complexes; mitochondrial biology; mitochondrial protein import; protein–lipid interactions

DOI: https://doi.org/10.1016/j.tibs.2025.03.011