Mitoribosome dysfunction in sensorineural hearing loss: genetic mechanisms and clinical implication.
4 affiliations
- 1Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
- 2Center for Mitochondrial Biomedicine and Department of Otolaryngology-Head and Neck Surgery, the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China.
- 3Institute of Genetics, Zhejiang University, Hangzhou, Zhejiang, China.
- 4Center for Genetic Medicine, Zhejiang University International Institute and School of Medicine, Yiwu, Zhejiang, China.
Abstract
Mitochondrial translation depends on coordinated contributions from the mitochondrial and nuclear genomes and is essential for oxidative phosphorylation. Disruption of this system can cause isolated sensorineural hearing loss or auditory impairment within multisystem disease. This review examines how mitochondrial rRNA variants, nuclear-encoded mitoribosomal protein defects, and environmental exposures converge on mitochondrial translation to impair hearing. The mitochondrial 12S rRNA 1555A>G and 1494C>T mutations alter decoding-site architecture and increase susceptibility to aminoglycoside ototoxicity, whereas pathogenic variants in nuclear mitoribosomal protein genes can compromise subunit assembly, stability, or abundance. Nuclear modifiers, particularly TRMU, and secondary mitochondrial tRNA variants illustrate how RNA modification and tRNA function influence the consequences of a primary rRNA defect. We propose mitochondrial translational reserve as a testable framework for incomplete penetrance and cochlear vulnerability, while recognizing that its quantitative relationship to hearing outcomes remains unresolved. Current clinical applications include molecular diagnosis, genotype-informed aminoglycoside prescribing, cascade testing of maternal relatives, and individualized hearing rehabilitation. Patient-derived auditory models and genetic rescue studies provide opportunities to clarify disease mechanisms and evaluate interventions, although modifier correction and pharmacological otoprotection remain experimental. Integrating molecular mechanisms with clinical assessment can strengthen prevention of avoidable ototoxicity and guide care for mitochondrial hearing loss.
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BibTeX
@article{cai2026mitoribosome,
title = {{Mitoribosome dysfunction in sensorineural hearing loss: genetic mechanisms and clinical implication.}},
author = {Luhang Cai and Chao Chen and Jia Chen and Jianguo He and Min-Xin Guan},
journal = {Journal of otology},
year = {2026},
month = oct,
doi = {10.26599/joto.2026.9540084},
url = {https://europepmc.org/article/MED/42996637},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Mitoribosome dysfunction in sensorineural hearing loss: genetic mechanisms and clinical implication.
AU - Luhang Cai
AU - Chao Chen
AU - Jia Chen
AU - Jianguo He
AU - Min-Xin Guan
PY - 2026
DA - 2026/10/01
JO - Journal of otology
DO - 10.26599/joto.2026.9540084
UR - https://europepmc.org/article/MED/42996637
AB - Mitochondrial translation depends on coordinated contributions from the mitochondrial and nuclear genomes and is essential for oxidative phosphorylation. Disruption of this system can cause isolated sensorineural hearing loss or auditory impairment within multisystem disease. This review examines how mitochondrial rRNA variants, nuclear-encoded mitoribosomal protein defects, and environmental exposures converge on mitochondrial translation to impair hearing. The mitochondrial 12S rRNA 1555A>G and 1494C>T mutations alter decoding-site architecture and increase susceptibility to aminoglycoside ototoxicity, whereas pathogenic variants in nuclear mitoribosomal protein genes can compromise subunit assembly, stability, or abundance. Nuclear modifiers, particularly TRMU, and secondary mitochondrial tRNA variants illustrate how RNA modification and tRNA function influence the consequences of a primary rRNA defect. We propose mitochondrial translational reserve as a testable framework for incomplete penetrance and cochlear vulnerability, while recognizing that its quantitative relationship to hearing outcomes remains unresolved. Current clinical applications include molecular diagnosis, genotype-informed aminoglycoside prescribing, cascade testing of maternal relatives, and individualized hearing rehabilitation. Patient-derived auditory models and genetic rescue studies provide opportunities to clarify disease mechanisms and evaluate interventions, although modifier correction and pharmacological otoprotection remain experimental. Integrating molecular mechanisms with clinical assessment can strengthen prevention of avoidable ototoxicity and guide care for mitochondrial hearing loss.
SN - 1672-2930
SN - 2524-1753
ER -