The Import of the Transcription Factor STAT3 into Mitochondria Depends on GRIM-19, a Component of the Electron Transport Chain
The Import of the Transcription Factor STAT3 into Mitochondria Depends on GRIM-19, a Component of the Electron Transport Chain
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DOI：
10.1074/jbc.m112.378984
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发表时间：
2013-02-15
影响因子：
4.8
通讯作者：
Sepuri, Naresh Babu Venkata
中科院分区：
文献类型：
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作者：
Tammineni, Prasad;Anugula, Chandrashekhar;Sepuri, Naresh Babu Venkata
信号转导子和转录激活子3（STAT 3）是一种核转录因子，也存在于线粒体中，并以不依赖于转录的方式调节细胞呼吸。STAT 3进入线粒体的机制仍然不清楚。在这份报告中，我们表明，线粒体定位STAT 3驻留在线粒体内膜。体外导入研究表明，与类维生素A干扰素相关的基因诱导细胞死亡19（GRIM-19），一种复合物I亚基，作为伴侣将STAT 3招募到线粒体中。此外，GRIM-19增强STAT 3整合到复合物I中。STAT 3中的S727 A突变即使在GRIM-19存在的情况下也会减少其输入和组装。总之，我们的研究揭示了GRIM-19在STAT 3招募到线粒体中的新伴侣功能。
The signal transducer and activator of transcription 3 (STAT3), a nuclear transcription factor, is also present in mitochondria and regulates cellular respiration in a transcriptional-independent manner. The mechanism of STAT3 import into mitochondria remains obscure. In this report we show that mitochondrial-localized STAT3 resides in the inner mitochondrial membrane. In vitro import studies show that the gene associated with retinoid interferon induced cell mortality 19 (GRIM-19), a complex I subunit that acts as a chaperone to recruit STAT3 into mitochondria. In addition, GRIM-19 enhances the integration of STAT3 into complex I. A S727A mutation in STAT3 reduces its import and assembly even in the presence of GRIM-19. Together, our studies unveil a novel chaperone function for GRIM-19 in the recruitment of STAT3 into mitochondria.