Human copper chaperone for superoxide dismutase 1 mediates its own oxidation-dependent import into mitochondria
Human copper chaperone for superoxide dismutase 1 mediates its own oxidation-dependent import into mitochondria
复制标题
DOI：
10.1038/ncomms3430
复制
发表时间：
2013-09
影响因子：
16.6
通讯作者：
Yutaka Suzuki;M. Ali;M. Fischer;J. Riemer
中科院分区：
文献类型：
--
作者：
Yutaka Suzuki;M. Ali;M. Fischer;J. Riemer
氧化应激可由多种细胞系统抵消，包括铜锌超氧化物歧化酶1 （SOD1）及其激活伴侣，即SOD1的铜伴侣（CCS1）。这两种酶在结构上是相关的，并且都定位于细胞质和线粒体膜间空间，在那里它们特异性地抵消线粒体衍生的超氧化物。人类CCS1转运到线粒体的机制在很大程度上尚不清楚。在这里，我们表明CCS1的输入取决于线粒体中成熟CCS1的存在。在输入过程中，在CCS1中通过依赖CCS1的反应形成二硫键。我们证明了氧化和进口依赖于CCS1中位置227和141/144的半胱氨酸残基的存在。值得注意的是，CCS1导入与SOD1导入相似，也依赖于CCS1。我们的观察结果表明，CCS1在线粒体中作为一种特殊的进口受体，促进了SOD1和CCS1的进口和折叠，从而扩大了线粒体膜间空间氧化依赖性蛋白进口的底物谱。
Oxidative stress is counteracted by various cellular systems, including copper–zinc superoxide dismutase 1 (SOD1) and its activating chaperone, that is, the copper chaperone for SOD1 (CCS1). Both enzymes are structurally related, and both localize to the cytosol and the mitochondrial intermembrane space where they specifically counteract mitochondria-derived superoxide. The mechanism by which human CCS1 is transported into mitochondria is largely unclear. Here we show that CCS1 import depends on the presence of mature CCS1 in the mitochondria. During import, a disulphide bond is formed in CCS1 in a CCS1-dependent reaction. We demonstrate that oxidation and import depend on the presence of cysteine residues at positions 227 and 141/144 in CCS1. Notably, CCS1 import parallels SOD1 import that also depends on CCS1. Our observations suggest that CCS1 serves as a specialized import receptor in mitochondria that facilitates the import and folding of SOD1 and CCS1, thereby extending the substrate spectrum of oxidation-dependent protein import in the mitochondrial intermembrane space.