Leary Scot C, Winge Dennis R, Cobine Paul A
Montreal Neurological Institute and McGill University, Montreal, Canada H3A 2B4.
Biochim Biophys Acta. 2009 Jan;1793(1):146-53. doi: 10.1016/j.bbamcr.2008.05.002. Epub 2008 May 15.
Mitochondria contain two enzymes, Cu,Zn superoxide dismutase (Sod1) and cytochrome c oxidase (CcO), that require copper as a cofactor for their biological activity. The copper used for their metallation originates from a conserved, bioactive pool contained within the mitochondrial matrix, the size of which changes in response to either genetic or pharmacological manipulation of cellular copper status. Its dynamic nature implies molecular mechanisms exist that functionally couple mitochondrial copper handling with other, extramitochondrial copper trafficking pathways. The recent finding that mitochondrial proteins with established roles in CcO assembly can also effect changes in cellular copper levels by modulating copper efflux from the cell supports a mechanistic link between organellar and cellular copper metabolism. However, the proteins and molecular mechanisms that link trafficking of copper to and from the organelle with other cellular copper trafficking pathways are unknown. This review documents our current understanding of copper trafficking to, and within, the mitochondrion for metallation of CcO and Sod1; the pathways by which the two copper centers in CcO are formed; and, the interconnections between mitochondrial function and the regulation of cellular copper homeostasis.
线粒体含有两种酶，即铜锌超氧化物歧化酶（Sod1）和细胞色素c氧化酶（CcO），它们需要铜作为其生物活性的辅助因子。用于它们金属化的铜源自线粒体基质中一个保守的生物活性库，其大小会根据细胞铜状态的基因或药理学操作而变化。其动态性质意味着存在分子机制，将线粒体铜处理与其他线粒体外铜运输途径在功能上联系起来。最近的发现表明，在CcO组装中具有既定作用的线粒体蛋白也可以通过调节细胞铜外流来影响细胞铜水平，这支持了细胞器和细胞铜代谢之间的机制联系。然而，将铜进出细胞器的运输与其他细胞铜运输途径联系起来的蛋白质和分子机制尚不清楚。本综述记录了我们目前对铜运输到线粒体以及在线粒体内用于CcO和Sod1金属化的理解；CcO中两个铜中心形成的途径；以及线粒体功能与细胞铜稳态调节之间的相互联系。
