Horn Darryl, Al-Ali Hassan, Barrientos Antoni
Department of Biochemistry & Molecular Biology, The John T. MacDonald Foundation Center for Medical Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Mol Cell Biol. 2008 Jul;28(13):4354-64. doi: 10.1128/MCB.01920-07. Epub 2008 Apr 28.
Copper is an essential cofactor of two mitochondrial enzymes: cytochrome c oxidase (COX) and Cu-Zn superoxide dismutase (Sod1p). Copper incorporation into these enzymes is facilitated by metallochaperone proteins which probably use copper from a mitochondrial matrix-localized pool. Here we describe a novel conserved mitochondrial metallochaperone-like protein, Cmc1p, whose function affects both COX and Sod1p. In Saccharomyces cerevisiae, Cmc1p localizes to the mitochondrial inner membrane facing the intermembrane space. Cmc1p is essential for full expression of COX and respiration, contains a twin CX9C domain conserved in other COX assembly copper chaperones, and has the ability to bind copper(I). Additionally, mutant cmc1 cells display increased mitochondrial Sod1p activity, while CMC1 overexpression results in decreased Sod1p activity. Our results suggest that Cmc1p could play a direct or indirect role in copper trafficking and distribution to COX and Sod1p.
细胞色素c氧化酶（COX）和铜锌超氧化物歧化酶（Sod1p）。金属伴侣蛋白促进铜掺入这些酶中，这些蛋白可能利用线粒体基质定位池中的铜。在这里，我们描述了一种新型的保守的线粒体金属伴侣样蛋白Cmc1p，其功能影响COX和Sod1p。在酿酒酵母中，Cmc1p定位于面向膜间隙的线粒体内膜。Cmc1p对于COX的完全表达和呼吸是必需的，包含在其他COX组装铜伴侣中保守的双CX9C结构域，并且具有结合铜（I）的能力。此外，突变的cmc1细胞显示线粒体Sod1p活性增加，而CMC1过表达导致Sod1p活性降低。我们的结果表明，Cmc1p可能在铜向COX和Sod1p的运输和分布中起直接或间接作用。
