Increased mitochondrial DNA copy number protects hair cells and HEI‑OC1 cells against drug‑induced apoptosis

Mei,Honglin; Mei,Dongmei; Yu,Huiqian; Sun,Shan; Chen,Yan; Zhang,Yanping; Chai,Renjie; Li,Huawei

doi:10.3892/mmr.2019.10838

Increased mitochondrial DNA copy number protects hair cells and HEI‑OC1 cells against drug‑induced apoptosis

Authors:
- Honglin Mei
- Dongmei Mei
- Huiqian Yu
- Shan Sun
- Yan Chen
- Yanping Zhang
- Renjie Chai
- Huawei Li
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Affiliations: ENT Institute and Department of Otorhinolaryngology, Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200031, P.R. China, Department of Stomatology, Key Laboratory of Oral Clinical Medicine, The Affiliated Hospital of Qingdao University, College of Stomatology, Qingdao University, Qingdao, Shandong 266000, P.R. China, Co‑Innovation Center of Neuroregeneration, Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing, Jiangsu 210096, P.R. China
Published online on: November 20, 2019 https://doi.org/10.3892/mmr.2019.10838
Pages: 338-346
Copyright: © Mei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Several factors trigger apoptosis in cochlear hair cells. Previous studies have shown that mitochondria play key roles in apoptosis, but the role of mitochondrial deoxyribonucleic acid (mtDNA) copy number in the pathogenesis of hair cell apoptosis remains largely unknown. We used mouse cochlear hair cells and House Ear Institute‑Organ of Corti 1 (HEI‑OC1) cells to explore the relationship between mtDNA copy number and cell apoptosis. We found that the mtDNA copy number of hair cells was reduced relative to mitochondrial mass and hypothesized that increasing it might have a protective effect. We then increased the mtDNA copy number of the hair and HEI‑OC1 cells by transfecting them with an adeno‑associated virus (AAV) vector containing mitochondrial transcription factor A (TFAM). We found that the apoptosis rates decreased upon inducing apoptosis with neomycin or cisplatin (DDP). To elucidate the mechanisms, we analyzed the mitochondrial‑membrane permeability and mitochondrial function of HEI‑OC1 cells. Our results suggested that the increase in mtDNA copy number could protect hair cells and HEI‑OC1 cells against drug‑induced apoptosis by stabilizing the permeability of the mitochondrial membrane and mitochondrial function.

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