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Reduced mitophagy in the cochlea of aged C57BL/6J mice. 2020

Jeonghyun Oh, and Cha Kyung Youn, and Yonghyun Jun, and Eu-Ri Jo, and Sung Il Cho
Department of Otolaryngology-Head and Neck Surgery, Chosun University College of Medicine, Gwangju, South Korea.

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.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D011494 Protein Kinases A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. Protein Kinase,Kinase, Protein,Kinases, Protein
D003051 Cochlea The part of the inner ear (LABYRINTH) that is concerned with hearing. It forms the anterior part of the labyrinth, as a snail-like structure that is situated almost horizontally anterior to the VESTIBULAR LABYRINTH. Cochleas
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D063306 Mitophagy Proteolytic breakdown of the MITOCHONDRIA via autophagy. Mitochondrial Degradation

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