The p38 Pathway Regulates Oxidative Stress Tolerance by Phosphorylation of Mitochondrial Protein IscU
The p38 Pathway Regulates Oxidative Stress Tolerance by Phosphorylation of Mitochondrial Protein IscU
复制标题
p38 通路通过线粒体蛋白 IscU 磷酸化调节氧化应激耐受性
DOI：
10.1074/jbc.m114.589093
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发表时间：
2014-11-14
影响因子：
4.8
通讯作者：
Han, Jiahuai
中科院分区：
文献类型：
--
作者：
Tian, Lili;Chen, Jianming;Han, Jiahuai
背景：p38信号通路是一种进化上保守的信号通路，对多种应激反应均有应答。结果：dIscU可被dMK 2磷酸化，从而影响线粒体呼吸复合物I活性。结论：p38信号下游的铁硫簇蛋白IscU被MK2磷酸化可能调节氧化应激耐受。重要性：IscU是MK2的一种新型底物，首次将p38信号通路与线粒体铁硫簇连接起来，p38信号通路是一种进化上保守的信号通路，对多种应激都有反应。然而，其潜在机制在很大程度上尚不清楚。在本研究中，我们证明，p38 b是一个主要的p38 MAPK参与调节氧化应激耐受性除了p38 a和p38 c在果蝇。我们进一步显示了MK2作为p38激活的下游激酶在抗氧化应激中的重要性。此外，我们确定了铁-硫簇支架蛋白IscU作为MK2在果蝇细胞和哺乳动物细胞中的新底物。这些结果意味着p38通路和线粒体铁硫簇之间的新的机制连接。
Background: The p38 pathway is an evolutionarily conserved signaling pathway that responds to a variety of stresses. Results: dIscU can be phosphorylated by dMK2, thereby impacting mitochondrial respiratory complex I activity. Conclusion: Iron-sulfur cluster protein IscU phosphorylation by MK2 downstream of p38 signaling may regulate oxidative stress tolerance. Significance: IscU is a novel substrate of MK2, mechanistically connecting the p38 pathway and mitochondria iron-sulfur clusters for the first time.The p38 pathway is an evolutionarily conserved signaling pathway that responds to a variety of stresses. However, the underlying mechanisms are largely unknown. In the present study, we demonstrate that p38b is a major p38 MAPK involved in the regulation of oxidative stress tolerance in addition to p38a and p38c in Drosophila. We further show the importance of MK2 as a p38-activated downstream kinase in resistance to oxidative stresses. Furthermore, we identified the iron-sulfur cluster scaffold protein IscU as a new substrate of MK2 both in Drosophila cells and in mammalian cells. These results imply a new mechanistic connection between the p38 pathway and mitochondria iron-sulfur clusters.