Age-Related Hearing Loss in C57BL/6J Mice Is Associated with Mitophagy Impairment in the Central Auditory System

Youn, Cha Kyung; Jun, Yonghyun; Jo, Eu-Ri; Cho, Sung-Il

doi:10.3390/ijms21197202

Cited by 24 publications

(18 citation statements)

References 39 publications

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“…mRNA levels of BNIP3, PINK1, Parkin and NIX, and the protein levels of BNIP3, PINK1 and Parkin decrease in the mouse auditory cortex with aging [ 197 ];…”

Section: Figurementioning

confidence: 99%

Mitophagy and Oxidative Stress: The Role of Aging

et al. 2021

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Mitochondrial dysfunction is a hallmark of aging. Dysfunctional mitochondria are recognized and degraded by a selective type of macroautophagy, named mitophagy. One of the main factors contributing to aging is oxidative stress, and one of the early responses to excessive reactive oxygen species (ROS) production is the induction of mitophagy to remove damaged mitochondria. However, mitochondrial damage caused at least in part by chronic oxidative stress can accumulate, and autophagic and mitophagic pathways can become overwhelmed. The imbalance of the delicate equilibrium among mitophagy, ROS production and mitochondrial damage can start, drive, or accelerate the aging process, either in physiological aging, or in pathological age-related conditions, such as Alzheimer’s and Parkinson’s diseases. It remains to be determined which is the prime mover of this imbalance, i.e., whether it is the mitochondrial damage caused by ROS that initiates the dysregulation of mitophagy, thus activating a vicious circle that leads to the reduced ability to remove damaged mitochondria, or an alteration in the regulation of mitophagy leading to the excessive production of ROS by damaged mitochondria.

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“…mRNA levels of BNIP3, PINK1, Parkin and NIX, and the protein levels of BNIP3, PINK1 and Parkin decrease in the mouse auditory cortex with aging [ 197 ];…”

Section: Figurementioning

confidence: 99%

Mitophagy and Oxidative Stress: The Role of Aging

et al. 2021

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“…This occurrence may contribute to the cellular changes observed in an old central auditory system, resulting in age-related hearing loss. Thus, NIP3L/NIX may play a vital role in maintaining cochlear cell homeostasis during the aging process of the hearing system [37,38]. BNIP3L was detected at medium levels in all human samples, with strong expression in saccule paralleled by strong expression detected in all mouse cell types.…”

Section: Discussionmentioning

confidence: 94%

Hearing Function: Identification of New Candidate Genes Further Explaining the Complexity of This Sensory Ability

Concas

Morgan

Serra

et al. 2021

Genes

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To date, the knowledge of the genetic determinants behind the modulation of hearing ability is relatively limited. To investigate this trait, we performed Genome-Wide Association Study (GWAS) meta-analysis using genotype and audiometric data (hearing thresholds at 0.25, 0.5, 1, 2, 4, and 8 kHz, and pure-tone averages of thresholds at low, medium, and high frequencies) collected in nine cohorts from Europe, South-Eastern USA, Caucasus, and Central Asia, for an overall number of ~9000 subjects. Three hundred seventy-five genes across all nine analyses were tagged by single nucleotide polymorphisms (SNPs) reaching a suggestive p-value (p < 10−5). Amongst these, 15 were successfully replicated using a gene-based approach in the independent Italian Salus in the Apulia cohort (n = 1774) at the nominal significance threshold (p < 0.05). In addition, the expression level of the replicated genes was assessed in published human and mouse inner ear datasets. Considering expression patterns in humans and mice, eleven genes were considered particularly promising candidates for the hearing function: BNIP3L, ELP5, MAP3K20, MATN2, MTMR7, MYO1E, PCNT, R3HDM1, SLC9A9, TGFB2, and YTHDC2. These findings represent a further contribution to our understanding of the genetic basis of hearing function and its related diseases.

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“…Recent studies have found that mitophagy is decreased in ARHL (Oh et al, 2020;Youn et al, 2020). PHB2 has been regarded as the mitophagy receptor (Wei et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…He et al, 2017). However, recent studies have reported that mitophagy was reduced in aged cochlea and central auditory system, which could aggravate cellular damage and increase hearing loss (Oh et al, 2020;Youn et al, 2020). PINK1/Parkin have been identified as important proteins involved in mitophagy.…”

Section: Introductionmentioning

confidence: 99%

The expression of PHB2 in the cochlea: Possible relation to age‐related hearing loss

Guan

Shang

Teng

et al. 2021

Cell Biology International

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Age-related hearing loss (ARHL) is the most prevalent sensory deficit in the elderly, but its mechanism remains unclear. Scaffold protein prohibitin 2 (PHB2) has been widely involved in aging and neurodegeneration. However, the role of PHB2 in ARHL is undeciphered to date. To investigate the expression pattern and the role of PHB2 in ARHL, we used C57BL/6 mice and HEI-OC1 cell line as models. In our study, we have found PHB2 exists in the cochlea and is expressed in hair cells, spiral ganglion neurons, and HEI-OC1 cells. In mice with ARHL, mitophagy is reduced and correspondingly the expression level of PHB2 is decreased. Moreover, after H 2 O 2 treatment the mitophagy is activated and the PHB2 expression is increased. These findings indicate that PHB2 may exert an important role in ARHL through mitophagy. Findings from this study will be helpful for elucidating the mechanism underlying the ARHL and for providing a new target for ARHL treatment.

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Age-Related Hearing Loss in C57BL/6J Mice Is Associated with Mitophagy Impairment in the Central Auditory System

Cited by 24 publications

References 39 publications

Mitophagy and Oxidative Stress: The Role of Aging

Mitophagy and Oxidative Stress: The Role of Aging

Hearing Function: Identification of New Candidate Genes Further Explaining the Complexity of This Sensory Ability

The expression of PHB2 in the cochlea: Possible relation to age‐related hearing loss

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