内质网、线粒体、细胞核互作网络与钙离子调控机制研究
结题报告
批准号:
92054105
项目类别:
重大研究计划
资助金额:
80.0 万元
负责人:
贺号
依托单位:
学科分类:
细胞器及亚细胞结构、互作与功能
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
贺号
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中文摘要
内质网线粒体互作和钙离子调控是形成细胞钙信号的关键因素,对细胞多种发育和生理功能具有重要的影响;也是调节线粒体的生理病理状态的重要途径。内质网线粒体接触位点调控钙离子机制非常复杂,受到多种因素的影响,目前尚未阐明。内质网与核膜紧密连接,与线粒体一起形成互作网络,调节核内钙信号,影响多种细胞过程。由于缺少精准、孤立的研究方法,核内钙信号的形成规律尚不明确。本项目提出研发一种非侵入、精准的飞秒激光刺激方法,在亚微米毫秒的时空精度上调控细胞器钙释放,以研究内质网线粒体和细胞核/核膜的互作与钙调控机制。通过激光在微小时空尺度上可控调节钙释放和扩散过程,阐明接触位点调控内质网线粒体钙传输的关键分子和机制,揭示线粒体生理与分子状态对接触位点的影响,厘清细胞器互作网络对核内钙信号的调节规律。这对于细胞器互作机制和钙信号调控的研究,以及细胞生长、线粒体疾病等领域具有重要的理论和技术价值。
英文摘要
The interaction and calcium modulation between endoplasmic reticulum (ER) and mitochondria (mito) are key to the formation of cellular calcium signaling and significant to the development and physiology of cells. It is also important to the mitochondrial physiology and pathology. The mechanism of calcium modulation by ER-mito contact site is quite complex, influenced by many other factors and thus still elusive. The ER directly contacts with nuclear membrane (NM), forms the interaction network together with mito, and regulates nuclear calcium signaling for a lot of downstream cell processes. Due to the lack of precise and isolated approaches, the mechanism of nuclear calcium signaling formation is also unclear. In this proposal, a noninvasive and precise stimulation method by femtosecond laser will be developed to control the calcium release from organelles at the level of submicron and millisecond for the research of ER-mito-NM interaction and calcium modulation mechanism. By the controlled release of calcium at ultra-tiny spatial-temporal level, the key molecules and mechanism of ER-mito interaction and calcium transport will be clarified. The influence to contact sites by molecular and physiological status of mito will also be investigated. The calcium regulation in nucleus by the interaction network of organelles will also be studied. This research is of good theoretical and technical value to the research of organelle interaction and calcium modulation, and the cell growth and mitochondrial diseases as well.
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激光精准调控细胞钙离子通道技术与机制研究
  • 批准号:
    22ZR1430000
  • 项目类别:
    省市级项目
  • 资助金额:
    0.0万元
  • 批准年份:
    2022
  • 负责人:
    贺号
  • 依托单位:
飞秒激光刺激调控细胞核内钙离子水平的研究
  • 批准号:
    61975118
  • 项目类别:
    面上项目
  • 资助金额:
    63.0万元
  • 批准年份:
    2019
  • 负责人:
    贺号
  • 依托单位:
超快激光诱导干细胞分化研究
  • 批准号:
    81571719
  • 项目类别:
    面上项目
  • 资助金额:
    58.0万元
  • 批准年份:
    2015
  • 负责人:
    贺号
  • 依托单位:
国内基金
海外基金