Regulation of mitochondrial networks in hair cells of the zebrafish lateral line

项目总结 内耳功能障碍导致的听力障碍的治疗选择有限，没有永久性的 解决方案。在内耳内，耳蜗毛细胞对外界的侮辱和遗传特别敏感。 微扰。对毛细胞的高新陈代谢需求表明，它们可能容易受到 线粒体。目前的建议旨在评估毛细胞内线粒体的特征， 毛细胞维持一种独特的线粒体表型以适应其代谢需求的总体假设。 该提案使用斑马鱼侧线的毛细胞作为内耳毛细胞的模型系统。 通过这个项目，我已经证明了侧线毛细胞线粒体具有独特的表型， 细胞顶端有较小的线粒体，底部靠近突触带的网状网络。 该项目还测试了这种线粒体网络是否是毛细胞特有的，涉及哪些基因 维持这种表型，以及它是否受到机械转导的调节。这些研究方法 线粒体是新的，因为它们寻求定量地研究线粒体动力学(1)，当大多数 到目前为止，以往的研究依赖于主观分类和(2)三个维度。这样做的结果 该提案将为毛细胞维持其有效性提供新的见解，以及如何改变 亚细胞结构可能会导致听力受损或丧失。

PROJECT SUMMARY Hearing impairments resulting from inner ear dysfunction have limited treatment options and no permanent solution. Within the inner ear, hair cells of the cochlea are particularly sensitive to outside insult and genetic perturbations. The high metabolic demand on hair cells suggests they might be vulnerable to alterations in their mitochondria. The current proposal seeks to evaluate the characteristics of mitochondria within hair cells, with an overall hypothesis that hair cells maintain a unique mitochondrial phenotype to fit their metabolic demand. The proposal uses hair cells of the zebrafish lateral line as a model system for hair cells in the inner ear. Through this project, I have shown that lateral line hair cell mitochondria have a unique phenotype, with smaller mitochondria at the apical end of the cell, and reticular networks at the base, near the synaptic ribbons. The project also tested whether this mitochondrial network was specific to hair cells, what genes are involved in maintaining this phenotype, and if it is regulated by mechanotransduction. These approaches to studying mitochondria are novel in that they seek to study mitochondrial dynamics (1) quantitatively, when most previous studies to date rely on subjective classifications and (2) in three dimensions. The results of this proposal will provide new insights into what hair cells require to maintain their efficacy, and how changes in subcellular structures could result in hearing impairment or loss.