Department of Pediatrics, Clinical Sciences, Lund University, Lund, Sweden.
Mitochondrion. 2010 Aug;10(5):497-509. doi: 10.1016/j.mito.2010.05.009. Epub 2010 May 23.
A homozygous mutation in the complex III chaperone BCS1L causes GRACILE syndrome (intrauterine growth restriction, aminoaciduria, cholestasis, hepatic iron overload, lactacidosis). In control and patient fibroblasts we localized BCS1L in inner mitochondrial membranes. In patient liver, kidney, and heart BCS1L and Rieske protein levels, as well as the amount and activity of complex III, were decreased. Major histopathology was found in kidney and liver with cirrhosis and iron deposition, but of iron-related proteins only ferritin levels were high. In placenta from a GRACILE fetus, the ferrooxidases ceruloplasmin and hephaestin were upregulated suggesting association between iron overload and placental dysfunction.
一个导致 GRACILE 综合征（宫内生长受限、氨基酸尿、胆汁淤积、肝铁过载、乳酸性酸中毒）的 III 复合物接头蛋白 BCS1L 纯合突变。在对照和患者成纤维细胞中，我们将 BCS1L 定位在内线粒体膜上。在患者的肝、肾和心脏中，BCS1L 和 Rieske 蛋白水平以及 III 复合物的数量和活性均降低。主要组织病理学发现于肝硬化和铁沉积的肝和肾中，但仅铁相关蛋白中的铁蛋白水平升高。在 GRACILE 胎儿的胎盘中，上调了亚铁氧化酶 ceruloplasmin 和 hephaestin，提示铁过载与胎盘功能障碍之间的关联。
