Mitoribosome dysfunction in sensorineural hearing loss: genetic mechanisms and clinical implication
Year: 2026
Type: review
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.
Source: Journal of Otology
Language: English
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: diamond
Awards: G4339908002, 遗传性耳聋诊治新技术研究
OpenAlex ID: W7225157304