Mitochondrial-nuclear communication by prohibitin shuttling under oxidative stress.
Mitochondrial-nuclear communication by prohibitin shuttling under oxidative stress.
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DOI：
10.1021/bi2008933
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发表时间：
2011-10-04
期刊：
影响因子：
2.9
通讯作者：
Jahng WJ
中科院分区：
文献类型：
--
作者：
Sripathi SR;He W;Atkinson CL;Smith JJ;Liu Z;Elledge BM;Jahng WJ
线粒体-核通讯是在应激条件下维持线粒体活性的关键。线粒体-细胞核网络适应细胞内氧化和还原环境的变化对于视网膜和视网膜色素上皮（RPE）细胞的存活至关重要，因为它们需要高氧和快速代谢。然而，线粒体信号的产生和传递到细胞核仍然是难以捉摸的。在此之前，我们的体内研究表明，在衰老和糖尿病模型中，prohibition在视网膜中上调，而在RPE中下调。本研究采用脂质结合法、2D凝胶电泳法、免疫细胞化学、Western blot、敲低法等生化方法研究了禁止素在视网膜和RPE中的功能作用。siRNA的蛋白损耗表征了禁止蛋白是线粒体中的抗凋亡分子，而脂质结合实验则证明了氧化应激下线粒体和细胞核之间的亚细胞通讯。活性氧引起的线粒体禁止素的表达和定位变化对线粒体的完整性至关重要。我们认为，在视网膜和RPE的应激环境下，禁止蛋白作为抗凋亡分子和转录调节因子穿梭于线粒体和细胞核之间。
Mitochondrial-nuclear communication is critical to maintain mitochondrial activity under stress conditions. Adaptation of the mitochondria-nucleus network to changes in the intracellular oxidation and reduction milieu is critical for the survival of retinal and retinal pigment epithelial (RPE) cells, in relation to their high oxygen demand and rapid metabolism. However, the generation and transmittal of mitochondrial signal to the nucleus remains elusive. Previously, our in vivo study revealed that prohibitin is up-regulated in the retina but is down-regulated in RPE in the aging and diabetic model. In this study, the functional role of prohibitin in the retina and the RPE was studied using biochemical methods, including lipid binding assay, 2D gel electrophoresis, immunocytochemistry, Western blot, and knockdown approach. Protein depletion by siRNA characterized prohibitin as an anti-apoptotic molecule in mitochondria, while lipid binding assay demonstrated subcellular communications between mitochondria and the nucleus under oxidative stress. The changes of the expressions and localization of mitochondrial prohibitin triggered by reactive oxygen species are crucial for mitochondrial integrity. We propose that prohibitin shuttles between mitochondria and the nucleus as an anti-apoptotic molecule and a transcriptional regulator under stress environment in the retina and RPE.