Regulation of Mitochondrial DNA

线粒体 DNA 的调控

基本信息

  • 批准号:
    RGPIN-2016-04083
  • 负责人:
  • 金额:
    $ 2.62万
  • 依托单位:
  • 依托单位国家:
    加拿大
  • 项目类别:
    Discovery Grants Program - Individual
  • 财政年份:
    2016
  • 资助国家:
    加拿大
  • 起止时间:
    2016-01-01 至 2017-12-31
  • 项目状态:
    已结题

项目摘要

The role that mitochondria play in cellular function is increasingly being recognized by researchers. Mitochondria encode their own genome (mtDNA), a molecule that is essential for their function. Although first described over 50 years ago, many questions remain about how mtDNA is maintained and expressed. As a researcher studying the basic mechanisms regulating mitochondria, my newly established program will explore mtDNA regulation. In addition to traditional means of studying mitochondria and mtDNA, we will utilize novel methods we have developed to transfect DNA into mitochondria. Taking advantage of our expertise in mtDNA and mitochondrial cell biology, the proposed research comprises three aims with an overall goal of understanding how proteins and sequence elements regulate mtDNA. Aim 1: To determine how the balanced expression of mtDNA is controlled The relative rates of transcription from the three mitochondrial promoters balances mitochondrial gene expression, mtDNA replication, and mitochondrial ribosome biogenesis. We will determine how the relative rates of mitochondrial transcription are regulated by examining the roles of mitochondrial transcription factors and mtDNA sequences. Additionally, we will examine how signaling pathways affecting mitochondrial transcription alter the balance of mitochondrial expression and also determine the functional consequences of altering this balance. Aim 2: To test the role of mtDNA sequence elements in cells Our novel methods for transfecting DNA into mitochondria allow us for the first time to test the cellular relevance of mtDNA sequence elements. Instead of directly manipulating mtDNA, which is currently not possible, we will transfect a plasmid containing mtDNA regulatory elements, which can be engineered. Determining which structural elements are required for the maintenance of this plasmid will lead to novel understanding about how the mtDNA is regulated. Aim 3: To uncover novel roles of nuclear transcription factors in mitochondria While nuclear transcription factors (NTFs) have been reported in mitochondria, their roles remain largely undefined. Whether NTFs play a direct role in mitochondrial transcription is a matter of debate, as it is difficult to separate their nuclear and mitochondrial functions. We will test this issue by targeting these transcription factors directly to mitochondria and determining their effects on mitochondrial function. Novelty and Significance Our studies, which are an extension of our previously work, will advance our basic understanding of mitochondrial function by answering fundamental questions about the regulation of mtDNA. Improving our basic understanding of mitochondria will have an impact at both the cellular and organismal level and is also relevant to animal health. This research program will also provide a training venue for the next wave of mitochondrial researchers.
线粒体在细胞功能中的作用越来越多地被研究人员所认识。线粒体编码自己的基因组(mtDNA),这是一种对其功能至关重要的分子。虽然在50多年前首次描述,但关于mtDNA如何维持和表达的许多问题仍然存在。作为一名研究线粒体调控基本机制的研究人员,我新设立的项目将探索线粒体DNA的调控。除了研究线粒体和mtDNA的传统方法外,我们还将利用我们开发的新方法将DNA插入线粒体。利用我们在mtDNA和线粒体细胞生物学方面的专业知识,拟议的研究包括三个目标,总体目标是了解蛋白质和序列元件如何调节mtDNA。 目的1:探讨线粒体DNA平衡表达的调控机制 三种线粒体启动子的相对转录速率平衡线粒体基因表达、mtDNA复制和线粒体核糖体生物合成。我们将通过研究线粒体转录因子和mtDNA序列的作用来确定线粒体转录的相对速率是如何调节的。此外,我们将研究影响线粒体转录的信号通路如何改变线粒体表达的平衡,并确定改变这种平衡的功能后果。 目的2:探讨线粒体DNA序列元件在细胞中的作用 我们将DNA导入线粒体的新方法使我们首次能够测试mtDNA序列元件的细胞相关性。我们将不直接操作mtDNA,而是直接转染一个含有mtDNA调控元件的质粒,这是目前不可能的。确定维持这种质粒所需的结构元件将导致对mtDNA如何调节的新的理解。 目的3:揭示线粒体核转录因子的新功能 虽然核转录因子(NTFs)已被报道在线粒体中,它们的作用仍然在很大程度上不确定。NTFs是否在线粒体转录中发挥直接作用是一个有争议的问题,因为很难将它们的核功能和线粒体功能分开。我们将通过将这些转录因子直接靶向线粒体并确定它们对线粒体功能的影响来测试这个问题。 新奇与意义 我们的研究是我们以前工作的延伸,将通过回答有关mtDNA调控的基本问题来推进我们对线粒体功能的基本理解。提高我们对线粒体的基本理解将在细胞和生物体水平上产生影响,也与动物健康有关。这项研究计划还将为下一波线粒体研究人员提供培训场所。

项目成果

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Shutt, Timothy其他文献

The intracellular redox state is a core determinant of mitochondrial fusion
  • DOI:
    10.1038/embor.2012.128
  • 发表时间:
    2012-10-01
  • 期刊:
  • 影响因子:
    7.7
  • 作者:
    Shutt, Timothy;Geoffrion, Michele;McBride, Heidi M.
  • 通讯作者:
    McBride, Heidi M.

Shutt, Timothy的其他文献

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{{ truncateString('Shutt, Timothy', 18)}}的其他基金

Regulation of Mitochondrial DNA
线粒体 DNA 的调控
  • 批准号:
    RGPIN-2016-04083
  • 财政年份:
    2022
  • 资助金额:
    $ 2.62万
  • 项目类别:
    Discovery Grants Program - Individual
Live-Cell Super-Resolution Imaging of Dynamic Cellular Processes
动态细胞过程的活细胞超分辨率成像
  • 批准号:
    RTI-2023-00050
  • 财政年份:
    2022
  • 资助金额:
    $ 2.62万
  • 项目类别:
    Research Tools and Instruments
Regulation of Mitochondrial DNA
线粒体 DNA 的调控
  • 批准号:
    RGPIN-2016-04083
  • 财政年份:
    2021
  • 资助金额:
    $ 2.62万
  • 项目类别:
    Discovery Grants Program - Individual
Regulation of Mitochondrial DNA
线粒体 DNA 的调控
  • 批准号:
    RGPIN-2016-04083
  • 财政年份:
    2019
  • 资助金额:
    $ 2.62万
  • 项目类别:
    Discovery Grants Program - Individual
Regulation of Mitochondrial DNA
线粒体 DNA 的调控
  • 批准号:
    RGPIN-2016-04083
  • 财政年份:
    2018
  • 资助金额:
    $ 2.62万
  • 项目类别:
    Discovery Grants Program - Individual
Regulation of Mitochondrial DNA
线粒体 DNA 的调控
  • 批准号:
    RGPIN-2016-04083
  • 财政年份:
    2017
  • 资助金额:
    $ 2.62万
  • 项目类别:
    Discovery Grants Program - Individual

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线粒体 DNA 的调控
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线粒体 DNA 的调控
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Regulation of Mitochondrial DNA
线粒体 DNA 的调控
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    RGPIN-2016-04083
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REGULATION OF MITOCHONDRIAL DNA-MEDIATED SIGNALING AND ITS CONTRIBUTION TO CELLULAR AND ORGANISMAL AGING
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Regulation of Mitochondrial DNA
线粒体 DNA 的调控
  • 批准号:
    RGPIN-2016-04083
  • 财政年份:
    2018
  • 资助金额:
    $ 2.62万
  • 项目类别:
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