ArticleNucleic acids research2025
Context-specific inhibition of mitochondrial ribosomes by phenicol and oxazolidinone antibiotics.
Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Halting translation by the letter with sequence-selective small molecules.Nature chemical biology · 2026Review
- Cortical organoids reveal human-specific role of METTL5 in neurodevelopment via regulation of CHCHD2.Stem cell reports · 2026Article
- A multilayered stress-response circuit: The mammalian mitochondrial UPR.The FEBS journal · 2026Review
- "Lariocidin and ribosome-targeting lasso peptides as emerging antimicrobial agents against multidrug-resistant bacteria".The Journal of antibiotics · 2026Review
- Approaches for Studying Context Specificity of Translation Inhibitor Action.International journal of molecular sciences · 2026Review
- Off-target anti-leukemic effects of antibiotics: mechanisms and therapeutic insights.Cancer chemotherapy and pharmacology · 2026Review
- Membrane insertion of mitochondrial-encoded proteins regulates ribosome decoding speed.Nature structural & molecular biology · 2026Article
- Structural modification of oxazolidinone antibiotics alters nascent peptide stalling preference and peptide trajectory through the ribosome.bioRxiv : the preprint server for biology · 2026Article
- How tailored Ribo-seq methods probe unique translation events.RNA (New York, N.Y.) · 2026Review
- Discovery and development of a new oxazolidinone with reduced toxicity for the treatment of tuberculosis.Nature medicine · 2026Article
- Design, Synthesis and Biological Evaluation of New Oxazolidinone Antimicrobial Agents with Low Monoamine Oxidase A Inhibition.Drug design, development and therapy · 2026Article
- Synthesis and antibacterial activity of novel benzodioxin-containing oxazolidinones against M. abscessus.Bioorganic & medicinal chemistry letters · 2025Article
- Hybrid Antibiotics Targeting the Bacterial Ribosome.ACS central science · 2025Article
- Prodrug florfenicol amine is activated by intrinsic resistance to target Mycobacterium abscessus.Nature microbiology · 2025Article
- Linezolid in the Focus of Antimicrobial Resistance ofInternational journal of molecular sciences · 2025Review
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9 authors.
Funding
Abstract
The antibiotics chloramphenicol (CHL) and oxazolidinones, including linezolid (LZD), are known to inhibit mitochondrial translation. This can result in serious, potentially deadly, side effects when used therapeutically. Although the mechanism by which CHL and LZD inhibit bacterial ribosomes has been elucidated in detail, their mechanism of action against mitochondrial ribosomes has yet to be explored. CHL and oxazolidinones bind to the ribosomal peptidyl transfer center (PTC) of the bacterial ribosome and prevent incorporation of incoming amino acids under specific sequence contexts, causing ribosomes to stall only at certain sequences. Through mitoribosome profiling, we show that inhibition of mitochondrial ribosomes is similarly context-specific-CHL and LZD lead to mitoribosome stalling primarily when there is an alanine, serine, or threonine in the penultimate position of the nascent peptide chain. We further validate context-specific stalling through in vitro translation assays. A high-resolution cryo-electron microscopy structure of LZD bound to the PTC of the human mitoribosome shows extensive similarity to the mode of bacterial inhibition and also suggests potential avenues for altering selectivity. Our findings could help inform the rational development of future, less mitotoxic, antibiotics, which are critically needed in the current era of increasing antimicrobial resistance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.