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Review Open Access

VDAC1: The mitochondrial gatekeeper in the battle against hearing loss (Review)

  • Authors:
    • Zhong-Jia Ding
    • Yin Wang
  • View Affiliations / Copyright

    Affiliations: Department of Otolaryngology, Xijing Hospital, Air Force Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Ultrasound Medicine, Xi'an Daxing Hospital, Xi'an, Shaanxi 710016, P.R. China
    Copyright: © Ding et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 184
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    Published online on: September 26, 2025
       https://doi.org/10.3892/br.2025.2062
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Abstract

The development of hearing loss is strongly associated with mitochondrial damage, particularly downstream of mitochondrial autophagy, which is a process that is coincidentally key for selectively removing damaged mitochondria. Voltage‑dependent anion channel 1 (VDAC1) is an important protein in the mitochondrial outer membrane that regulates various essential biological processes, including energy metabolism, calcium ion transport and cell apoptosis. VDAC1 can bidirectionally regulate cell fate, where its oligomerization can exacerbate oxidative stress, leading to cell damage and even death. By contrast, its ubiquitination supports cell survival by regulating mitochondrial autophagy, thereby improving mitochondrial quality control. VDAC1 can significantly contribute to the prevention and management of hearing loss. The present review summarizes how the ubiquitination and oligomerization modifications of VDAC1 can balance cell survival and death, while also exploring current hypotheses on mechanisms associated with hearing loss. These findings emphasize the research prospects of VDAC1 as a novel target for hearing loss treatment.
View Figures

Figure 1

Hypothetical diagram illustrating the
effect of VDAC1 on the fate of cochlear cells under noise
stimulation. The regulation of VDAC1 ubiquitination by the E3
ubiquitin ligase CHIP may lead to different fates of cochlear
sensory cells. First, increased VDAC1 ubiquitination leads to
mitochondrial autophagy, and mitochondrial quality control mediates
the clearance of damage factors and cell survival. Second,
decreased VDAC1 ubiquitination mediates VDAC1 oligomerization in
the outer mitochondrial membrane, leading to abnormal opening of
the mitochondrial permeability transition pore, the release of
apoptotic factors, mitochondrial rupture, and cell apoptosis. The
figure was created using Figdraw 2.0 Online Drawing Platform;
https://www.figdraw.com/#/. VDAC1,
voltage-dependent anion channel 1; CHIP, carboxy terminus of
HSP-70-interacting protein; UBA52, ubiquitin A-52 residue ribosomal
protein fusion product 1.
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Spandidos Publications style
Ding Z and Wang Y: VDAC1: The mitochondrial gatekeeper in the battle against hearing loss (Review). Biomed Rep 23: 184, 2025.
APA
Ding, Z., & Wang, Y. (2025). VDAC1: The mitochondrial gatekeeper in the battle against hearing loss (Review). Biomedical Reports, 23, 184. https://doi.org/10.3892/br.2025.2062
MLA
Ding, Z., Wang, Y."VDAC1: The mitochondrial gatekeeper in the battle against hearing loss (Review)". Biomedical Reports 23.6 (2025): 184.
Chicago
Ding, Z., Wang, Y."VDAC1: The mitochondrial gatekeeper in the battle against hearing loss (Review)". Biomedical Reports 23, no. 6 (2025): 184. https://doi.org/10.3892/br.2025.2062
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Spandidos Publications style
Ding Z and Wang Y: VDAC1: The mitochondrial gatekeeper in the battle against hearing loss (Review). Biomed Rep 23: 184, 2025.
APA
Ding, Z., & Wang, Y. (2025). VDAC1: The mitochondrial gatekeeper in the battle against hearing loss (Review). Biomedical Reports, 23, 184. https://doi.org/10.3892/br.2025.2062
MLA
Ding, Z., Wang, Y."VDAC1: The mitochondrial gatekeeper in the battle against hearing loss (Review)". Biomedical Reports 23.6 (2025): 184.
Chicago
Ding, Z., Wang, Y."VDAC1: The mitochondrial gatekeeper in the battle against hearing loss (Review)". Biomedical Reports 23, no. 6 (2025): 184. https://doi.org/10.3892/br.2025.2062
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