bims-tricox 2025-03-09 papers

Issue of 2025–03–09
four papers selected by
Yash Verma, University of Zurich

J Cell Biol. 2025 Apr 07. pii: e202407110. [Epub ahead of print]224(4):

Cytoplasmic ribosomes on mitochondria alter the local membrane environment for protein import.

Ya-Ting Chang, Benjamin A Barad, Juliette Hamid, Hamidreza Rahmani, Brian M Zid, Danielle A Grotjahn.

Most of the mitochondria proteome is nuclear-encoded, synthesized by cytoplasmic ribosomes, and targeted to the mitochondria posttranslationally. However, a subset of mitochondrial-targeted proteins is imported co-translationally, although the molecular mechanisms governing this process remain unclear. We employ cellular cryo-electron tomography to visualize interactions between cytoplasmic ribosomes and mitochondria in Saccharomyces cerevisiae. We use surface morphometrics tools to identify a subset of ribosomes optimally oriented on mitochondrial membranes for protein import. This allows us to establish the first subtomogram average structure of a cytoplasmic ribosome at the mitochondrial surface in the native cellular context, which showed three distinct connections with the outer mitochondrial membrane surrounding the peptide exit tunnel. Further, this analysis demonstrated that cytoplasmic ribosomes primed for mitochondrial protein import cluster on the outer mitochondrial membrane at sites of local constrictions of the outer and inner mitochondrial membranes. Overall, our study reveals the architecture and the spatial organization of cytoplasmic ribosomes at the mitochondrial surface, providing a native cellular context to define the mechanisms that mediate efficient mitochondrial co-translational protein import.

DOI: https://doi.org/10.1083/jcb.202407110

Philos Trans R Soc Lond B Biol Sci. 2025 Mar 06. 380(1921): 20230381

High-throughput approaches for the identification of ribosome heterogeneity.

Edwin S Kyei-Baffour, Qi Chang Lin, Ferhat Alkan, William J Faller.

Recent advances in the fields of RNA translation and ribosome biology have demonstrated the heterogeneous nature of ribosomes. This manifests not only across different cellular contexts but also within the same cell. Such variations in ribosomal composition, be it in ribosomal RNAs or proteins, can significantly influence cellular processes and responses by altering the mRNAs being translated or the dynamics of ribosomes during the translation process. Therefore, identifying this heterogeneity is crucial for unravelling the complexity of gene expression across different fields of biology. Here we provide an overview of recent advances in high-throughput techniques for identifying ribosomal heterogeneity. We cover methodologies for probing both rRNA and protein components of the ribosome and encompass the most recent next-generation sequencing and computational analyses, as well as a diverse array of mass spectrometry techniques.This article is part of the discussion meeting issue 'Ribosome diversity and its impact on protein synthesis, development and disease'.

Keywords: high-throughput techniques; rRNA; ribosomal proteins; ribosome heterogeneity

DOI: https://doi.org/10.1098/rstb.2023.0381

Science. 2025 Mar 07. 387(6738): eadn2623

A subcellular map of translational machinery composition and regulation at the single-molecule level.

Zijian Zhang, Adele Xu, Yunhao Bai, Yuxiang Chen, Kitra Cates, Craig Kerr, Abel Bermudez, Teodorus Theo Susanto, Kelsie Wysong, Fernando J García Marqués, Garry P Nolan, Sharon Pitteri, Maria Barna.

Millions of ribosomes are packed within mammalian cells, yet we lack tools to visualize them in toto and characterize their subcellular composition. In this study, we present ribosome expansion microscopy (RiboExM) to visualize individual ribosomes and an optogenetic proximity-labeling technique (ALIBi) to probe their composition. We generated a super-resolution ribosomal map, revealing subcellular translational hotspots and enrichment of 60S subunits near polysomes at the endoplasmic reticulum (ER). We found that Lsg1 tethers 60S to the ER and regulates translation of select proteins. Additionally, we discovered ribosome heterogeneity at mitochondria guiding translation of metabolism-related transcripts. Lastly, we visualized ribosomes in neurons, revealing a dynamic switch between monosomes and polysomes in neuronal translation. Together, these approaches enable exploration of ribosomal localization and composition at unprecedented resolution.

DOI: https://doi.org/10.1126/science.adn2623

NPJ Metab Health Dis. 2025 ;3(1): 6

Pulling back the mitochondria's iron curtain.

Shani Ben Zichri-David, Liraz Shkuri, Tslil Ast.

Mitochondrial functionality and cellular iron homeostasis are closely intertwined. Mitochondria are biosynthetic hubs for essential iron cofactors such as iron-sulfur (Fe-S) clusters and heme. These cofactors, in turn, enable key mitochondrial pathways, such as energy and metabolite production. Mishandling of mitochondrial iron is associated with a spectrum of human pathologies ranging from rare genetic disorders to common conditions. Here, we review mitochondrial iron utilization and its intersection with disease.

Keywords: Biochemistry; Cell biology; Metabolic pathways

DOI: https://doi.org/10.1038/s44324-024-00045-y