Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Japan.
Department of Otolaryngology-Head and Neck Surgery, Osaka Metropolitan University, Japan.
FEBS Open Bio. 2023 Jul;13(7):1365-1374. doi: 10.1002/2211-5463.13655. Epub 2023 Jun 6.
Previous studies have revealed that age-related hearing loss (AHL) in Cdk5 regulatory subunit-associated protein 1 (Cdk5rap1)-knockout mice is associated with pathology in the cochlea. Here, we aimed to identify mitochondrial alterations in the cochlea of Cdk5rap1-knockout mice with AHL. Mitochondria in the spiral ganglion neurons (SGNs) and hair cells (HCs) were normal despite senescence; however, the mitochondria of types I, II, and IV spiral ligament fibrocytes were ballooned, damaged, and ballooned, respectively, in the stria vascularis. Our results suggest that the accumulation of dysfunctional mitochondria in the lateral wall, rather than the loss of HCs and SGNs, leads to the onset of AHL. Our results provide valuable information regarding the underlying mechanisms of AHL and the relationship between aberrant tRNA modification-induced hearing loss and mitochondrial dysfunction.
先前的研究表明，Cdk5 调节亚单位相关蛋白 1（Cdk5rap1）敲除小鼠的年龄相关性听力损失（AHL）与耳蜗病理学有关。在这里，我们旨在确定 AHL 中 Cdk5rap1 敲除小鼠耳蜗中的线粒体改变。尽管衰老，但螺旋神经节神经元（SGNs）和毛细胞（HCs）中的线粒体正常；然而，I 型、II 型和 IV 型螺旋韧带成纤维细胞的线粒体分别出现气球样变、损伤和气球样变。我们的结果表明，外侧壁中功能失调的线粒体积累而不是 HCs 和 SGNs 的丧失导致 AHL 的发生。我们的结果为 AHL 的潜在机制以及异常 tRNA 修饰诱导的听力损失与线粒体功能障碍之间的关系提供了有价值的信息。
