Mitochondrial cysteine desulfurase

线粒体半胱氨酸脱硫酶

基本信息

  • 批准号:
    7937766
  • 负责人:
  • 金额:
    $ 33.16万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-09-30 至 2012-08-31
  • 项目状态:
    已结题

项目摘要

Cysteine desulfurases perform essential functions in releasing sulfur from cysteine, forming a covalent persulfide, and channeling the persulfide sulfur to biologically critical recipients e.g. ironsulfur (Fe-S) clusters and thiolated tRNAs. The activity of cysteine desulfurase cannot be replaced by exogenously supplied sulfide or by other sulfur metabolizing enzymes, and thus cysteine desulfurase is essential for cell viability. The eukaryotic cysteine desulfurase is encoded by a single nuclear gene and is found primarily in mitochondria. In Saccharomyces cerevisiae mitochondria, the cysteine desulfurase protein Nfs1 is assembled in a large protein complex with a recently identified special accessory protein called Isd11. We found that Isd11 is required for Nfs1 cysteine desulfurase activity. Thus, Nfs1 and Isd11 expressed together in bacteria are assembled into an active complex, while these components expressed separately are inactive. Here we propose to characterize the active Nfs1/Isd11 complex, and regulation of its cysteine desulfurase activity by Fe-S cluster scaffold proteins, Isu. Aim 1 is to determine the role of yeast Isd11 in the active Nfs1/Isd11 cysteine desulfurase complex. Experiments will be performed using bacterial expressed and purified proteins, and also in a more physiological context using isolated intact mitochondria. Aim 2 is to characterize formation of persulfide sulfur on Nfs1/Isd11 in isolated intact mitochondria, with focus on the regulatory effect of the D37A mutation of Isu. The significance derives from the essential role of cysteine desulfurase for viability of all human cells. The enzyme is found primarily in mitochondria and is required for Fe-S cluster synthesis and tRNA thiolation in mitochondria, both are essential processes. The identification of specific diseases arising from defective Fe-S cluster assembly (e.g. Friedreich's ataxia, sideroblastic anemia, and mitochondrial myopathy) represents the tip of the iceberg. The recent discovery of a key role of Fe-S clusters in DNA repair and genome stability suggests that cysteine desulfurases are involved in these processes.
半胱氨酸脱硫酶从半胱氨酸中释放硫,形成硫

项目成果

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ANDREW B. DANCIS其他文献

ANDREW B. DANCIS的其他文献

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{{ truncateString('ANDREW B. DANCIS', 18)}}的其他基金

Mitochondria-cytoplasm interactions for cytosolic Fe-S cluster assembly
细胞质 Fe-S 簇组装的线粒体-细胞质相互作用
  • 批准号:
    10390734
  • 财政年份:
    2014
  • 资助金额:
    $ 33.16万
  • 项目类别:
Mitochondria-cytoplasm interactions for cytosolic Fe-S cluster assembly
细胞质 Fe-S 簇组装的线粒体-细胞质相互作用
  • 批准号:
    8883624
  • 财政年份:
    2014
  • 资助金额:
    $ 33.16万
  • 项目类别:
Mitochondria-cytoplasm interactions for cytosolic Fe-S cluster assembly
细胞质 Fe-S 簇组装的线粒体-细胞质相互作用
  • 批准号:
    10341169
  • 财政年份:
    2014
  • 资助金额:
    $ 33.16万
  • 项目类别:
Mitochondria-cytoplasm interactions for cytosolic Fe-S cluster assembly
细胞质 Fe-S 簇组装的线粒体-细胞质相互作用
  • 批准号:
    10571937
  • 财政年份:
    2014
  • 资助金额:
    $ 33.16万
  • 项目类别:
Mitochondria-cytoplasm interactions for cytosolic Fe-S cluster assembly
细胞质 Fe-S 簇组装的线粒体-细胞质相互作用
  • 批准号:
    8692127
  • 财政年份:
    2014
  • 资助金额:
    $ 33.16万
  • 项目类别:
Biochemistry and genetics of iron transport in mitochondria and related processes
线粒体铁转运及相关过程的生物化学和遗传学
  • 批准号:
    7891077
  • 财政年份:
    2009
  • 资助金额:
    $ 33.16万
  • 项目类别:
2007 Cell Biology of Metals Gordon Research Conference
2007年金属细胞生物学戈登研究会议
  • 批准号:
    7276348
  • 财政年份:
    2007
  • 资助金额:
    $ 33.16万
  • 项目类别:
USE OF DISTINCT IRON UPTAKE SYSTEMS BY CANDIDA ALBICANS
白色念珠菌使用独特的铁吸收系统
  • 批准号:
    6859406
  • 财政年份:
    2004
  • 资助金额:
    $ 33.16万
  • 项目类别:
USE OF DISTINCT IRON UPTAKE SYSTEMS BY CANDIDA ALBICANS
白色念珠菌使用独特的铁吸收系统
  • 批准号:
    6723856
  • 财政年份:
    2004
  • 资助金额:
    $ 33.16万
  • 项目类别:
USE OF DISTINCT IRON UPTAKE SYSTEMS BY CANDIDA ALBICANS
白色念珠菌使用独特的铁吸收系统
  • 批准号:
    7371105
  • 财政年份:
    2004
  • 资助金额:
    $ 33.16万
  • 项目类别:

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