The Redox Environment in the Mitochondrial Intermembrane Space Is Maintained Separately from the Cytosol and Matrix
The Redox Environment in the Mitochondrial Intermembrane Space Is Maintained Separately from the Cytosol and Matrix
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线粒体膜间隙中的氧化还原环境与细胞质和基质是分开的
DOI：
10.1074/jbc.m803028200
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发表时间：
2008-10-24
影响因子：
4.8
通讯作者：
Outten, Caryn E.
中科院分区：
文献类型：
--
作者：
Hu, Jingjing;Dong, Lixue;Outten, Caryn E.
线粒体中的氧化还原控制对于这个细胞器的正常运作是必不可少的。线粒体氧化还原过程的破坏导致了一系列人类疾病，包括癌症、神经退行性疾病和衰老。为了更好地表征该细胞器中的氧化还原调控途径，我们将基于绿色荧光蛋白的氧化还原传感器定位于酵母线粒体的膜间隙(IMS)和基质。这种方法使我们能够分别监控基质和IMS的氧化还原状态，提供了这两个隔室中氧化还原过程的更详细的图景。为了验证传感器对局部的谷胱甘肽(GSH)氧化还原变化的反应，我们使用氧化的GSH(GSSG)还原酶定位突变体来遗传操纵亚细胞的氧化还原状态。这些研究表明，胞质和基质中的氧化还原控制分别由胞质和线粒体GSSG还原酶亚型维持。我们的研究还表明，线粒体IMS的氧化作用比胞浆和线粒体基质强得多，不受内源性GSSG还原酶活性的直接影响。这些氧化还原测量被用来预测输入到IMS中的含有硫醇的蛋白质的氧化状态。
Redox control in the mitochondrion is essential for the proper functioning of this organelle. Disruption of mitochondrial redox processes contributes to a host of human disorders, including cancer, neurodegenerative diseases, and aging. To better characterize redox control pathways in this organelle, we have targeted a green fluorescent protein-based redox sensor to the intermembrane space (IMS) and matrix of yeast mitochondria. This approach allows us to separately monitor the redox state of the matrix and the IMS, providing a more detailed picture of redox processes in these two compartments. To verify that the sensors respond to localized glutathione (GSH) redox changes, we have genetically manipulated the subcellular redox state using oxidized GSH (GSSG) reductase localization mutants. These studies indicate that redox control in the cytosol and matrix are maintained separately by cytosolic and mitochondrial isoforms of GSSG reductase. Our studies also demonstrate that the mitochondrial IMS is considerably more oxidizing than the cytosol and mitochondrial matrix and is not directly influenced by endogenous GSSGreductase activity. These redox measurements are used to predict the oxidation state of thiol-containing proteins that are imported into the IMS.