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Review
. 2023 Mar 31:14:1176881.
doi: 10.3389/fphar.2023.1176881. eCollection 2023.

Mitochondrial redox system: A key target of antioxidant therapy to prevent acquired sensorineural hearing loss

Jeong-In Baek  1 , Ye-Ri Kim  2   3 , Kyu-Yup Lee  4 , Un-Kyung Kim  2   5
Affiliations
Review

Mitochondrial redox system: A key target of antioxidant therapy to prevent acquired sensorineural hearing loss

Jeong-In Baek et al. Front Pharmacol. .

Abstract

Noise (noise-induced hearing loss), and ototoxic drugs (drug-induced ototoxicity), and aging (age-related hearing loss) are the major environmental factors that lead to acquired sensorineural hearing loss. So far, there have been numerous efforts to develop protective or therapeutic agents for acquired hearing loss by investigating the pathological mechanisms of each types of hearing loss, especially in cochlear hair cells and auditory nerves. Although there is still a lack of information on the underlying mechanisms of redox homeostasis and molecular redox networks in hair cells, an imbalance in mitochondrial reactive oxygen species (ROS) levels that enhance oxidative stress has been suggested as a key pathological factor eventually causing acquired sensorineural hearing loss. Thus, various types of antioxidants have been investigated for their abilities to support auditory cells in maintenance of the hearing function against ototoxic stimuli. In this review, we will discuss the scientific possibility of developing drugs that target particular key elements of the mitochondrial redox network in prevention or treatment of noise- and ototoxic drug-induced hearing loss.

Keywords: ROS; acquired hearing loss; drug development; mitochondria; noise; ototoxic drugs.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Noise, aging and ototoxic drug-induced intracellular signaling pathways leading to hair cell death. It indicates that organelle stress (ER and mitochondria), inflammation, MAPK signaling pathways induced by three environmental stimuli are all mutually interact each other, which finally leads to apoptosis or necroptosis of hair cells. Importantly, increase in mitochondrial ROS is at the center of all the pathways.
FIGURE 2
FIGURE 2
Mitochondrial ROS-induced damages causing mitochondrial dysfunction. Direct damages of mitochondrial DNA and antioxidant enzyme, or disruption of ion homeostasis 1), or malfunction of the mitochondrial respiration system 2), can cause increase in mitochondrial ROS. It subsequently leads to increase in mitochondrial membrane potential 3) with depolarization of membrane potential 4), causing osmotic swelling of mitochondria and release of pro-apoptotic factors 5). Finally, cell death signaling pathways are activated by these apoptotic factors.
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Grants and funding

This research was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (Ministry of Science and ICT): RS-2023-00212674 (to J-IB), NRF-2020R1A2C2003529 (to K-YL), and NRF-2021R1C1C2006677 (to Y-RK). It was also supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT), No. 2022M3E5F2017487 (to U-KK).

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