Using the Zebrafish Lateral Line to Understand the Roles of Mitochondria in Sensorineural Hearing Loss.

Using the Zebrafish Lateral Line to Understand the Roles of Mitochondria in Sensorineural Hearing Loss.
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DOI:
10.3389/fcell.2020.628712
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发表时间:
2020
影响因子:
5.5
通讯作者:
Sheets L
Sheets L
中科院分区:
生物学2区
文献类型:
--
作者:
Holmgren M;Sheets L

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毛细胞是内耳的机械感受器,并且可以被噪声、老化和耳毒性药物损伤。这种损伤通常会导致永久性感音神经性听力损失。毛细胞具有高能量需求并且依赖于线粒体来产生ATP以及有助于细胞内钙稳态。除了产生ATP外,线粒体还产生活性氧,这可以导致氧化应激,并调节细胞死亡途径。斑马鱼侧线毛细胞在结构上和功能上类似于耳蜗毛细胞,但在完整的标本中是光学和生物学可访问的,使得斑马鱼成为研究毛细胞线粒体活性的良好模型。此外,斑马鱼胚胎的遗传操作的便利性允许研究与人类耳聋有关的突变,以及生成转基因模型,以可视化活生物体中的线粒体钙瞬变和线粒体活性。对斑马鱼侧线的研究表明,线粒体活性的变化可以预测毛细胞对氨基糖苷类或噪音暴露的敏感性。此外,抗氧化剂已被证明可以防止噪音创伤和耳毒性药物引起的毛细胞死亡。在这篇综述中,我们讨论了工具和最近的调查结果,斑马鱼毛细胞线粒体和他们参与细胞过程中,无论是在稳态条件下,并在噪音或耳毒性药物。斑马鱼侧线是研究线粒体在毛细胞病理中的作用和开发预防人类感音神经性听力损失的治疗策略的有价值的模型。
Hair cells are the mechanosensory receptors of the inner ear and can be damaged by noise, aging, and ototoxic drugs. This damage often results in permanent sensorineural hearing loss. Hair cells have high energy demands and rely on mitochondria to produce ATP as well as contribute to intracellular calcium homeostasis. In addition to generating ATP, mitochondria produce reactive oxygen species, which can lead to oxidative stress, and regulate cell death pathways. Zebrafish lateral-line hair cells are structurally and functionally analogous to cochlear hair cells but are optically and pharmacologically accessible within an intact specimen, making the zebrafish a good model in which to study hair-cell mitochondrial activity. Moreover, the ease of genetic manipulation of zebrafish embryos allows for the study of mutations implicated in human deafness, as well as the generation of transgenic models to visualize mitochondrial calcium transients and mitochondrial activity in live organisms. Studies of the zebrafish lateral line have shown that variations in mitochondrial activity can predict hair-cell susceptibility to damage by aminoglycosides or noise exposure. In addition, antioxidants have been shown to protect against noise trauma and ototoxic drug–induced hair-cell death. In this review, we discuss the tools and findings of recent investigations into zebrafish hair-cell mitochondria and their involvement in cellular processes, both under homeostatic conditions and in response to noise or ototoxic drugs. The zebrafish lateral line is a valuable model in which to study the roles of mitochondria in hair-cell pathologies and to develop therapeutic strategies to prevent sensorineural hearing loss in humans.
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