PGC-1α overexpression promotes mitochondrial biogenesis to protect auditory cells against cisplatin-induced cytotoxicity

Abstract

Cisplatin (CDDP)-induced ototoxicity is one of the common adverse effects of cisplatin chemotherapy. Thus far, effective approaches for attenuating hearing loss are unavailable in clinical practice. Mitochondrial biogenesis acts as a master element of mitochondrial health and is necessary for mitochondrial quality control. The current study examined whether mitochondrial biogenesis is involved in CDDP-induced ototoxicity. Herein, we showed that CDDP damaged mitochondrial function and caused death of House Ear Institute- Organ of Corti 1 (HEI-OC1) cells by impairing mitochondrial biogenesis. Moreover, overexpression of peroxisome proliferator-activated receptor-γ coactivator-1α, a key factor in mitochondrial biogenesis, promoted mitochondrial biogenesis in HEI-OC1 cells and protected them against CDDP-induced cytotoxicity. These findings suggest that mitochondrial biogenesis is involved in the pathology of CDDP cytotoxicity of HEI-OC1 cells, and activation of peroxisome proliferator-activated receptor-γ coactivator-1α can be considered a potential therapeutic strategy to attenuate CDDP-mediated ototoxicity. Key words: PGC-1α; cisplatin; mitochondrial biogenesis; survival; cell death; ZLN005; therapy; HEI-OC1 cells