Signal transducer and activator of transcription-1 localizes to the mitochondria and modulates mitophagy.
Signal transducer and activator of transcription-1 localizes to the mitochondria and modulates mitophagy.
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DOI：
10.4161/jkst.25666
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发表时间：
2013-10-01
期刊：
影响因子：
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通讯作者：
McCormick J
中科院分区：
文献类型：
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作者：
Bourke LT;Knight RA;Latchman DS;Stephanou A;McCormick J
信号转导子和转录激活子（STAT）蛋白是潜在的转录因子，其已被证明参与细胞增殖、发育、凋亡和自噬。STAT蛋白通过酪氨酸701和丝氨酸727处的磷酸化进行活化，在那里它们易位到细胞核以调节基因表达。STAT 1已被证明参与促进响应于心脏缺血/再灌注的凋亡细胞死亡，并且我们的实验室最近已证明参与负调节自噬。这些过程被认为促进细胞死亡并限制细胞存活，导致梗死的产生。在这里，我们提出的数据表明，STAT 1定位于线粒体和免疫共沉淀与LC 3。此外，电子显微镜研究还揭示了来自离体I/R处理的STAT 1 KO小鼠心脏的线粒体包含在双膜自噬体内，表明STAT 1可能参与负调节线粒体自噬。这是第一次描述STAT 1被定位于线粒体，也有一个作用，在线粒体自噬。
The signal transducer and activator of transcription (STAT) proteins are latent transcription factors that have been shown to be involved in cell proliferation, development, apoptosis, and autophagy. STAT proteins undergo activation by phosphorylation at tyrosine 701 and serine 727 where they translocate to the nucleus to regulate gene expression. STAT1 has been shown to be involved in promoting apoptotic cell death in response to cardiac ischemia/reperfusion and has recently been shown by our laboratory to be involved in negatively regulating autophagy. These processes are thought to promote cell death and restrict cell survival leading to the generation of an infarct. Here we present data that shows STAT1 localizes to the mitochondria and co-immunoprecipitates with LC3. Furthermore, electron microscopy studies also reveal mitochondria from ex vivo I/R treated hearts of STAT1KO mice contained within a double membrane autophagosome indicating that STAT1 may be involved in negatively regulating mitophagy. This is the first description of STAT1 being localized to the mitochondria and also having a role in mitophagy.