Cell Metabolism：两携铜蛋白可能与铜离子调控有关

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Cell Metabolism：两携铜蛋白可能与铜离子调控有关 铜（Copper）是人体的必要元素，许多含铜蛋白(copper-containingproteins)对于人体的生长或神经发育，扮演十分重要的角色。麦基尔大学（McGillUniversity）蒙特娄神经科学院（MontrealNeurologicalInstitute，MNI）的科学家发现，SCO1以及SCO2这两个携铜蛋白(copper-carryingproteins)，可能与铜离子的调控有

  生物谷报道：铜（Copper）是人体的必要元素，许多含铜蛋白(copper-containing proteins)对于人体的生长或神经发育，扮演十分重要的角色。麦基尔大学（McGill University）蒙特娄神经科学院（Montreal Neurological Institute，MNI）的科学家发现，SCO1以及SCO2这两个携铜蛋白(copper-carrying proteins)，可能与铜离子的调控有关，此研究发表于《细胞代谢》（Cell Metabolism）期刊。

  Eric Shoubridge教授说：“铜是维持细胞健康生长的重要元素，当铜离子的调节失常，会引发人体的许多疾病，包括：肝、肾、脑部或眼疾等。此外，铜离子也在器官早期发育中扮演重要的角色，研究人员发现SCO1以及SCO2这两个携铜蛋白的突变，也会导致许多新生儿疾病。”

  研究人员表示：粒腺体中的细胞色素C氧化酶（cytochrome coxidase，简称COX）也需要铜离子来维持其活性，而SCO1及SCO2正好就是组成COX的重要次单元（subunit）。这个蛋白质复合体在粒腺体的电子传递链中，是产生能量不可或缺的蛋白质。为了了解SCO1及SCO2的功能性，Shoubridge教授及其研究团队观察了含有突变型SCO1及SCO2的细胞，结果发现这两个蛋白具有维持不同细胞间铜离子平衡的功能，除了证明SCO1及SCO2具有双重功能外，这项发现也将对许多神经性疾病的治疗有所帮助。

  实际上该作者自从2004年以来就对相关蛋白进行了深入地研究。

Cell Metabolism, Vol 5, 9-20, January 2007

Article

The Human Cytochrome c Oxidase Assembly Factors SCO1 and SCO2 Have Regulatory Roles in the Maintenance of Cellular Copper Homeostasis
Scot C. Leary,1,2 Paul A. Cobine,3 Brett A. Kaufman,1,2 Guy-Hellen Guercin,1,2 Andre Mattman,4 Jan Palaty,4 Gillian Lockitch,4 Dennis R. Winge,3 Pierre Rustin,5 Rita Horvath,6 and Eric A. Shoubridge1,2,

1 Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada
2 Department of Human Genetics, McGill University, Montreal, QC H3A 2B4, Canada
3 Department of Medicine and Department of Biochemistry, University of Utah Health Sciences Center, Salt Lake City, UT 84132, USA
4 Department of Pathology and Laboratory Medicine, Children's & Women's Health Centre of British Columbia, Vancouver, BC V6H 3N1, Canada
5 Faculty of Medicine Denis Diderot, INSERM U676 and University of Paris 7, 75019 Paris, France
6 Metabolic Disease Centre Munich-Schwabing and Institute of Clinical Chemistry, Molecular Diagnostics and Mitochondrial Genetics, 80804 Munich, Germany


Corresponding author
Eric A. Shoubridge
eric@ericpc.mni.mcgill.ca

Summary

Human SCO1 and SCO2 are metallochaperones that are essential for the assembly of the catalytic core of cytochrome c oxidase (COX). Here we show that they have additional, unexpected roles in cellular copper homeostasis. Mutations in either SCO result in a cellular copper deficiency that is both tissue and allele specific. This phenotype can be dissociated from the defects in COX assembly and is suppressed by overexpression of SCO2, but not SCO1. Overexpression of a SCO1 mutant in control cells in which wild-type SCO1 levels were reduced by shRNA recapitulates the copper-deficiency phenotype in SCO1 patient cells. The copper-deficiency phenotype reflects not a change in high-affinity copper uptake but rather a proportional increase in copper efflux. These results suggest a mitochondrial pathway for the regulation of cellular copper content that involves signaling through SCO1 and SCO2, perhaps by their thiol redox or metal-binding state.