Metformin-induced mitophagy suppresses auditory hair cell apoptosis via AMPK pathway
Hearing loss is a pervasive issue affecting numerous individuals, and its etiology and categorization are multifaceted. Among these, sensorineural hearing loss (SNHL) emerges as the most prevalent variant among these. The primary causative factor underlying SNHL resides in the depletion of auditory...
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Elsevier
2025-02-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923025000267 |
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| author | Yifan Lai Jiawei Qiu Kuang Zheng Xiang Li Yinuo Lin Zhengzheng Li Haiqiu Sun |
| author_facet | Yifan Lai Jiawei Qiu Kuang Zheng Xiang Li Yinuo Lin Zhengzheng Li Haiqiu Sun |
| author_sort | Yifan Lai |
| collection | DOAJ |
| description | Hearing loss is a pervasive issue affecting numerous individuals, and its etiology and categorization are multifaceted. Among these, sensorineural hearing loss (SNHL) emerges as the most prevalent variant among these. The primary causative factor underlying SNHL resides in the depletion of auditory hair cells within the cochlea, yet the pursuit of efficacious therapeutic interventions remains an ongoing challenge. Previous investigations have illuminated the role of mitochondrial dysfunction in precipitating cellular apoptosis, and mitophagy has emerged as a promising mechanism to ameliorate such dysfunction. Additionally, it has been noted that metformin possesses the specific ability to induce mitophagy. Herein, our objective is to explore the protective effects of metformin-induced mitophagy against apoptosis in auditory hair cells (HEI-OC1 cells) and explore its potential mechanisms. Our results revealed that metformin effectively triggered mitophagy in HEI-OC1 cells. Moreover, metformin treatment showed the ability to prevent tert-butyl hydroperoxide (TBHP) induced mitochondrial dysfunction and intrinsic apoptotic pathways. Mechanistically, we discovered that metformin activates AMP-activated protein kinase (AMPK) signaling in HEI-OC1 cells stimulated by TBHP, thereby triggering mitophagy. Overall, our results suggest that metformin may represent a promising and innovative therapeutic strategy for mitigating the onset of hearing loss. |
| format | Article |
| id | doaj-art-aa6fdaf121e344579ac967aad9b4c38d |
| institution | Kabale University |
| issn | 1873-2747 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj-art-aa6fdaf121e344579ac967aad9b4c38d2025-02-07T04:46:45ZengElsevierBrain Research Bulletin1873-27472025-02-01221111214Metformin-induced mitophagy suppresses auditory hair cell apoptosis via AMPK pathwayYifan Lai0Jiawei Qiu1Kuang Zheng2Xiang Li3Yinuo Lin4Zhengzheng Li5Haiqiu Sun6Department of Otolaryngology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; The First Clinical Medical College of Wenzhou Medical University, Wenzhou, Zhejiang Province, ChinaThe Second Clinical Medical College of Wenzhou Medical University, Wenzhou, Zhejiang Province, ChinaDepartment of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, ChinaDepartment of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, ChinaDepartment of Cardiology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Corresponding authors.Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Corresponding authors.Department of Otolaryngology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Corresponding authors.Hearing loss is a pervasive issue affecting numerous individuals, and its etiology and categorization are multifaceted. Among these, sensorineural hearing loss (SNHL) emerges as the most prevalent variant among these. The primary causative factor underlying SNHL resides in the depletion of auditory hair cells within the cochlea, yet the pursuit of efficacious therapeutic interventions remains an ongoing challenge. Previous investigations have illuminated the role of mitochondrial dysfunction in precipitating cellular apoptosis, and mitophagy has emerged as a promising mechanism to ameliorate such dysfunction. Additionally, it has been noted that metformin possesses the specific ability to induce mitophagy. Herein, our objective is to explore the protective effects of metformin-induced mitophagy against apoptosis in auditory hair cells (HEI-OC1 cells) and explore its potential mechanisms. Our results revealed that metformin effectively triggered mitophagy in HEI-OC1 cells. Moreover, metformin treatment showed the ability to prevent tert-butyl hydroperoxide (TBHP) induced mitochondrial dysfunction and intrinsic apoptotic pathways. Mechanistically, we discovered that metformin activates AMP-activated protein kinase (AMPK) signaling in HEI-OC1 cells stimulated by TBHP, thereby triggering mitophagy. Overall, our results suggest that metformin may represent a promising and innovative therapeutic strategy for mitigating the onset of hearing loss.http://www.sciencedirect.com/science/article/pii/S0361923025000267MetforminHearing lossAutophagyMitophagyApoptosis |
| spellingShingle | Yifan Lai Jiawei Qiu Kuang Zheng Xiang Li Yinuo Lin Zhengzheng Li Haiqiu Sun Metformin-induced mitophagy suppresses auditory hair cell apoptosis via AMPK pathway Brain Research Bulletin Metformin Hearing loss Autophagy Mitophagy Apoptosis |
| title | Metformin-induced mitophagy suppresses auditory hair cell apoptosis via AMPK pathway |
| title_full | Metformin-induced mitophagy suppresses auditory hair cell apoptosis via AMPK pathway |
| title_fullStr | Metformin-induced mitophagy suppresses auditory hair cell apoptosis via AMPK pathway |
| title_full_unstemmed | Metformin-induced mitophagy suppresses auditory hair cell apoptosis via AMPK pathway |
| title_short | Metformin-induced mitophagy suppresses auditory hair cell apoptosis via AMPK pathway |
| title_sort | metformin induced mitophagy suppresses auditory hair cell apoptosis via ampk pathway |
| topic | Metformin Hearing loss Autophagy Mitophagy Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S0361923025000267 |
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