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Regulation and function of mitochondrial motility in neurons in vivo

体内神经元线粒体运动的调节和功能

基本信息

批准号：
10536402
负责人：
Eavan Jane Donovan
金额：
$ 4.59万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2025-06-30
项目状态：
未结题

项目摘要

Project Summary Mitochondria are dynamic organelles which support the metabolic needs of neurons across their entire lifetime. Previous research has sought to define the regulation of mitochondrial transport as dependent on the activity of the neuron, including changes in energy demand. However, previous studies and unpublished data from the Barnhart lab show mitochondrial motility is not dependent on neuronal activity. Given defects in mitochondrial transport have been implicated with neurodegeneration, the goal of this research is to elucidate the fundamental role of mitochondrial transport in maintaining healthy and functional neurons. I propose to define both in vivo mitochondrial localization across the neuron and contributions of mitochondrial motility in the function of the mitochondria in neurons. To define mitochondrial transport and function in vivo, I will use the Drosophila melanogaster visual system with live cell imaging using genetically encoded reporters of mitochondrial health and neuronal function. In Aim 1, I will use confocal microscopy, immunostaining and EM reconstructions to define the relationship between mitochondrial motility, mitochondrial distribution patterns and neuronal architecture. This aim will evaluate the relationship between neuronal structure and overall mitochondrial localization. In Aim 2, I will use mitochondrial perturbations to assess how mitochondrial motility affects mitochondrial health and neuronal function in vivo. These studies will define the regulation and functional relevance of mitochondrial motility in neurons, which paves the way towards future studies on the role of mitochondrial transport defects in disease, including in neurodegeneration.

项目摘要线粒体是一种动态的细胞器，它支持整个神经元的代谢需求。辈子以前的研究试图将线粒体转运的调节定义为依赖于线粒体的转运。神经元的活动，包括能量需求的变化。然而，以前的研究和未发表的数据来自巴恩哈特实验室的研究表明，线粒体运动并不依赖于神经元的活动。鉴于缺陷，线粒体转运与神经退行性变有关，本研究的目的是阐明线粒体运输在维持健康和功能性神经元中的基本作用。我建议定义了体内线粒体在神经元中的定位和线粒体运动在神经元中的作用。线粒体在神经元中的功能。为了定义体内线粒体的运输和功能，我将使用果蝇视觉系统与活细胞成像使用的基因编码的报告线粒体健康和神经元功能。在目标1中，我将使用共聚焦显微镜，免疫染色和 EM重建以确定线粒体运动、线粒体分布模式和神经元结构。这一目标将评估神经元结构与整体线粒体定位。在目标2中，我将使用线粒体扰动来评估线粒体运动影响体内线粒体健康和神经元功能。这些研究将确定神经元中线粒体运动的调节和功能相关性，为未来铺平了道路研究线粒体转运缺陷在疾病中的作用，包括在神经变性中的作用。