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Updated: Dec 21, 2025
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Published on: April 21, 2022
Reduced mitophagy in the cochlea of aged C57BL/6J mice
Jeonghyun Oh1, Cha Kyung Youn2, Yonghyun Jun3
1Department of Otolaryngology-Head and Neck Surgery, Chosun University College of Medicine, Gwangju, South Korea.
Abstract:
An increase in mitochondrial damage has been associated with a decline in the ability to mitigate damage through mitophagy in age-related pathologies. The present study aimed to investigate the changes of mitophagy in a mouse model with age-related hearing loss. C57BL/6J mice were divided into two groups: young (1 month) and aged (12 months). Hearing tests were conducted through the measurement of auditory brainstem response (ABR). Mitochondrial DNA copy number, the level of mitochondrial DNA damage, mitochondrial biogenesis, and mitophagy-related genes and proteins were investigated using real-time PCR and western blot analysis. Coexpression of mitophagosomes and lysosomes in the cochlea was investigated through immunofluorescence imaging analysis. Major players of mitophagy, Parkin and BNIP3, were also investigated through immunohistochemical staining in the cochlea. Hearing thresholds were observed to have increased in the aged group. The mitochondrial DNA copy number, PGC-1α, and PGC-1β significantly decreased in the cochlea of mice in the aged group. The mRNA levels of PINK1, Parkin, MUL1, Atg5, Atg12, Atg13, NIX, and BNIP3 significantly decreased in the cochlea of the mice in the aged group. The level of mitochondrial DNA damage significantly increased in the cochlea of mice in the aged group. Protein levels of PINK1, Parkin, BNIP3, COX4, LC3B, and all OXPHOS subunits significantly decreased in the cochlea of the mice in the aged group. Immunofluorescence imaging analysis of mitophagosomes and lysosomes revealed a decrease in the colocalization in the cochlea of mice in the aged group. Immunohistochemical imaging analysis of Parkin and BNIP3 revealed their decreased expression in aged cochlea. Our results indicate that reduced mitophagy with aging might be attributed to the cellular changes that occur in aged cochlea in the development of age-related hearing loss.
Insights
Reduced mitophagy, a cellular cleanup process, contributes to age-related hearing loss by increasing mitochondrial damage in the cochlea. This study highlights impaired mitophagy as a key factor in aging ears.
Area of Science:
- Cellular Biology
- Otolaryngology
- Gerontology
Background:
- Mitochondrial damage and impaired mitophagy are linked to age-related diseases.
- Age-related hearing loss (ARHL) is a growing concern with complex underlying mechanisms.
- Understanding cellular changes in the aging cochlea is crucial for ARHL research.
Purpose of the Study:
- To investigate the role of mitophagy in age-related hearing loss using a mouse model.
- To analyze changes in mitochondrial function and mitophagy markers in the cochlea of aged mice.
Main Methods:
- Auditory brainstem response (ABR) testing to assess hearing thresholds.
- Real-time PCR and Western blot to quantify mitochondrial DNA, damage, biogenesis, and mitophagy-related genes/proteins.
- Immunofluorescence and immunohistochemistry to visualize mitophagy markers (Parkin, BNIP3) and organelle colocalization in the cochlea.
Main Results:
- Aged mice exhibited increased hearing thresholds and elevated mitochondrial DNA damage.
- Key mitophagy-related genes (PINK1, Parkin, BNIP3) and proteins were significantly downregulated in aged cochlea.
- Reduced colocalization of mitophagosomes and lysosomes, along with decreased Parkin and BNIP3 expression, indicated impaired mitophagy in aged mice.
Conclusions:
- Age-related hearing loss is associated with significantly reduced mitophagy in the cochlea.
- Impaired mitochondrial quality control, specifically mitophagy, contributes to cellular dysfunction in aging ears.
- These findings suggest mitophagy as a potential therapeutic target for preventing or treating age-related hearing loss.
