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

斑马鱼侧线毛细胞线粒体网络的调节

• 批准号: 10455272
• 负责人: Andrea McQuate
• 金额: $ 1.76万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2021-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10455272
• 关键词: 3-Dimensional; Animals; Apical; Area; Biological Models; Buffers; CRISPR/Cas technology; Calcium; Cell Death; Cell physiology; Cells; Characteristics; Chronic; Classification; Cochlea; Communication impairment; Data; Dynamin; Electron Microscopy; Environment; Environmental Risk Factor; Exposure to; Face; Functional disorder; Genes; Genetic; Guanosine Triphosphate Phosphohydrolases; Hair Cells; Imaging Techniques; Inner Hair Cells; Inner mitochondrial membrane; Intervention; Labyrinth; Lead; Maintenance; Mediating; Membrane; Metabolic; Metabolism; Microscopy; Mitochondria; Morphology; Mutation; Neurons; OPA1 gene; Organelles; Outer Mitochondrial Membrane; Phenotype; Physiology; Play; Proteins; Regulation; Role; Series; Shapes; Specificity; Structure; Subcellular structure; Testing; Three-Dimensional Imaging; Zebrafish; base; cell injury; cell type; experimental study; fluorescence imaging; hearing impairment; insight; lateral line; mechanotransduction; mutant; novel; ribbon synapse

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.

项目摘要 内耳功能障碍导致的听力障碍的治疗选择有限， 溶液在内耳内，耳蜗的毛细胞对外部损伤和遗传损伤特别敏感。 扰动对毛细胞的高代谢需求表明，它们可能容易受到毛细胞结构改变的影响。 线粒体目前的建议旨在评估毛细胞内线粒体的特征， 毛细胞保持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，我已经表明，侧线毛细胞线粒体有一个独特的表型， 细胞顶端有较小的线粒体，基部有网状网络，靠近突触带。 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 在维持这种表型中，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，因为他们试图研究线粒体动力学（1）定量，当大多数 迄今为止，以往的研究依赖于主观分类和（2）在三个维度。的结果 该提案将为毛细胞维持其功效所需的内容以及毛细胞的变化提供新的见解。 亚细胞结构可能导致听力损伤或丧失。