BCL2 Interacting Protein 3-like/NIX-mediated Mitophagy Plays an Important Role in the Process of Age-related Hearing Loss. (10th February 2021)

• Record Type: Journal Article
• Authors: Kim, Yeon Ju; Choo, Oak-Sung; Lee, Jin-Sol; Jang, Jeong Hun; Woo, Hyun Goo; Choung, Yun-Hoon
• Is Part Of: Neuroscience. Volume 455(2021)
• Page Start: 39
• Page End: 51
• Publication Date: 2021-02-10
• Subjects: (BNIP3L)/NIX BCL2 interacting protein 3-like -- ABR Auditory brainstem response -- ARHL Age-related hearing loss -- DEG Differentially expressed genes -- DRP-1 Dynamin-related protein 1 -- FUNDC1 FUN14 domain containing 1 -- H&E Hematoxylin and Eosin -- H2O2 Hydrogen peroxide -- HCs Hair cells -- HEI-OC1 House Ear Institute-Organ of Corti 1 -- IHC Inner hair cell -- KEGG Kyoto Encyclopedia of Genes and Genomes -- LC3B Microtubule-associated protein 1 light chain 3 -- LW Lateral wall -- mPTP Mitochondrial permeability transition pore -- OHC Outer hair cell -- PINK1 PTEN-induced kinase 1 -- ROS Reactive oxygen species -- SA-β-gal Senescence-associated β-galactosidase -- SGCs Spiral ganglion cells -- siRNA Small interfering RNA -- SIRT1 Sirtuin 1 -- TEM Transmission electron microscopy; age-related hearing loss -- mitophagy -- BNIP3L/NIX -- hair cell -- spiral ganglion cell; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2020.12.005
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Damaged mitochondria are increased in hair cells and spiral ganglion cells in the ARHL, while mitophagy is not activated. Most transcripts associated with mitophagy were downregulated in an age-dependent manner. BNIP3L/NIX is significantly downregulated in vivo and in vitro with cellular senescence. Overexpression of BNIP3L/NIX alleviates cellular senescence by promoting mitochondrial protein degradation. Abstract: 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.