ArticleProceedings of the National Academy of Sciences of the United States of America2008
Genetic analysis of interactions with eukaryotic rRNA identify the mitoribosome as target in aminoglycoside ototoxicity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
103 citing papers in PubMed, 1 synthesis or guideline pooled it, 184 citations in OpenAlex.
- Increased risk of aminoglycoside-induced hearing loss in MDR-TB patients with HIV coinfection.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2018Pooled it
- Improvement of a Rapid and Highly Sensitive Method for the Diagnosis of the Mitochondrial m.1555A>G Mutation Based on a Single-Stranded Tag Hybridization Chromatographic Printed-Array Strip.Genetic testing and molecular biomarkers · 2021Trial
- Antibiotic-Induced Genotoxicity: Molecular Mechanisms, Cytogenetic Damage, and Implications for Human Health.International journal of molecular sciences · 2026Review
- Therapeutic potential of mitochondrial transfer in reversing mutant-to-wild-type mtDNA ratio and improving mitochondrial dysfunction in 1555A>G mtDNA mutation-associated hearing loss.Scientific reports · 2026Article
- The Role and Research Progress of Mitochondria in Sensorineural Hearing Loss.Molecular neurobiology · 2025Review
- Electrostatic Anchoring in RNA-Ligand Design─Dissecting the Effects of Positive Charges on Affinity, Selectivity, Binding Kinetics, and Thermodynamics.Journal of medicinal chemistry · 2025Article
- Recent advances in the biosynthetic pathway and structural modification of gentamicin.Frontiers in microbiology · 2025Review
- Mitochondrial-derived peptides, HNG and SHLP3, protect cochlear hair cells against gentamicin.Cell death discovery · 2024Article
- Multiple mechanisms of aminoglycoside ototoxicity are distinguished by subcellular localization of action.bioRxiv : the preprint server for biology · 2024Article
- Illuminating mitochondrial translation through mouse models.Human molecular genetics · 2024Review
- Multiple mechanisms of aminoglycoside ototoxicity are distinguished by subcellular localization of action.Frontiers in neurology · 2024Article
- Synthesis of Gentamicins C1, C2, and C2a and Antiribosomal and Antibacterial Activity of Gentamicins B1, C1, C1a, C2, C2a, C2b, and X2.ACS infectious diseases · 2023Article
- Synthesis of 4-Tetrahedron · 2023Article
- Our current understanding of the toxicity of altered mito-ribosomal fidelity during mitochondrial protein synthesis: What can it tell us about human disease?Frontiers in physiology · 2023Review
- Structural analysis of mitochondrial rRNA gene variants identified in patients with deafness.Frontiers in physiology · 2023Article
- Metabolic Labeling of Mitochondrial Translation Products in Whole Cells and Isolated Organelles.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Mitochondrial redox system: A key target of antioxidant therapy to prevent acquired sensorineural hearing loss.Frontiers in pharmacology · 2023Review
- Synthesis, Antibacterial and Antiribosomal Activity of the 3Antibiotics (Basel, Switzerland) · 2022Article
- Kanamycin and Cisplatin Ototoxicity: Differences in Patterns of Oxidative Stress, Antioxidant Enzyme Expression and Hair Cell Loss in the Cochlea.Antioxidants (Basel, Switzerland) · 2022Article
- Review
43 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aminoglycoside ototoxicity has been related to a surprisingly large number of cellular structures and metabolic pathways. The finding that patients with mutations in mitochondrial rRNA are hypersusceptible to aminoglycoside-induced hearing loss has indicated a possible role for mitochondrial protein synthesis. To study the molecular interaction of aminoglycosides with eukaryotic ribosomes, we made use of the observation that the drug binding site is a distinct domain defined by the small subunit rRNA, and investigated drug susceptibility of bacterial hybrid ribosomes carrying various alleles of the eukaryotic decoding site. Compared to hybrid ribosomes with the A site of human cytosolic ribosomes, susceptibility of mitochondrial hybrid ribosomes to various aminoglycosides correlated with the relative cochleotoxicity of these drugs. Sequence alterations that correspond to the mitochondrial deafness mutations A1555G and C1494T increased drug-binding and rendered the ribosomal decoding site hypersusceptible to aminoglycoside-induced mistranslation and inhibition of protein synthesis. Our results provide experimental support for aminoglycoside-induced dysfunction of the mitochondrial ribosome. We propose a pathogenic mechanism in which interference of aminoglycosides with mitochondrial protein synthesis exacerbates the drugs' cochlear toxicity, playing a key role in sporadic dose-dependent and genetically inherited, aminoglycoside-induced deafness.
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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.