Mitochondrial matrix copper complex used in metallation of cytochrome oxidase and superoxide dismutase
Mitochondrial matrix copper complex used in metallation of cytochrome oxidase and superoxide dismutase
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DOI：
10.1074/jbc.m606839200
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发表时间：
2006-12-01
影响因子：
4.8
通讯作者：
Winge, Dennis R.
中科院分区：
文献类型：
--
作者：
Cobine, Paul A.;Pierrel, Fabien;Winge, Dennis R.
线粒体基质铜配体（CuL）复合物，在哺乳动物细胞中保存，是可能的来源铜组装细胞色素c氧化酶（CcO）和超氧化物歧化酶1（SOD 1）在膜间隙（IMS）在酵母。将铜结合蛋白人类Sod 1和Crs 5靶向线粒体基质导致由CcO水平降低引起的不可发酵培养基上的生长障碍。这种作用被铜补充剂逆转。基质靶向Crs5减少了IMS内的Sod1蛋白，并损害了内膜束缚的人Sod1的活性。铜结合的基质靶向蛋白减弱的水平的CuL复合物，而不影响总线粒体铜。这些数据表明，通过异源竞争对手衰减的基质铜络合物限制了IMS内CcO和Sod1的代谢可用铜。配体也以表观的无金属状态存在于细胞质中。
A mitochondrial matrix copper ligand (CuL) complex, conserved in mammalian cells, is the likely source of copper for assembly of cytochrome c oxidase (CcO) and superoxide dismutase 1 (Sod1) within the intermembrane space (IMS) in yeast. Targeting the copper-binding proteins human Sod1 and Crs5 to the mitochondrial matrix results in growth impairment on non-fermentable medium caused by decreased levels of CcO. This effect is reversed by copper supplementation. Matrix-targeted Crs5 diminished Sod1 protein within the IMS and impaired activity of an inner membrane tethered human Sod1. Copper binding by the matrix-targeted proteins attenuates levels of the CuL complex without affecting total mitochondrial copper. These data suggest that attenuation of the matrix CuL complex via heterologous competitors limits available copper for metallation of CcO and Sod1 within the IMS. The ligand also exists in the cytoplasm in an apparent metal-free state.