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

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

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

Mol Med Rep. 2019 Nov 20;:

Authors: Mei H, Mei D, Yu H, Sun S, Chen Y, Zhang Y, Chai R, Li H

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.

PMID: 31939628 [PubMed - as supplied by publisher]