BCL2 Interacting Protein 3-like/NIX-mediated Mitophagy Plays an Important Role in the Process of Age-related Hearing Loss.

Clearance of dysfunctional mitochondria via mitophagy is essential for cell survival and cochlear functions. However, it is not clear which genes are significantly involved in this process. Here, we investigated the changes in mitophagy and mitophagy-associated genes in mouse auditory cells to determine a possible correlation between mitophagy and age-related hearing loss (ARHL). Here, we show that most transcripts associated with mitophagy were downregulated in an age-dependent manner. We identified one significant differentially expressed gene associated with mitophagy, BCL2 interacting protein 3-like (BNIP3L)/NIX. Mitophagy-inhibited cells with BNIP3L/NIX knockdown showed hyperresponsiveness to oxidative stress resulting in cell senescence with increased levels of TOMM20 and LC3B. Overexpression of BNIP3L/NIX promotes the degradation of TOMM20 and LC3B during premature cell senescence. In conclusion, BNIP3L/NIX may play an important role in mitochondria degradation maintaining cochlear cell homeostasis during the aging process of hearing.