Laboratoire de Biochimie, Hôpital de Bicêtre, Assistance Publique - Hôpitaux de Paris, 78 Rue du Général Leclerc, 94275 Le Kremlin Bicêtre Cedex, France.
Am J Hum Genet. 2013 Aug 8;93(2):384-9. doi: 10.1016/j.ajhg.2013.06.015. Epub 2013 Aug 1.
Many individuals with abnormalities of mitochondrial respiratory chain complex III remain genetically undefined. Here, we report mutations (c.288G>T [p.Trp96Cys] and c.643C>T [p.Leu215Phe]) in CYC1, encoding the cytochrome c1 subunit of complex III, in two unrelated children presenting with recurrent episodes of ketoacidosis and insulin-responsive hyperglycemia. Cytochrome c1, the heme-containing component of complex III, mediates the transfer of electrons from the Rieske iron-sulfur protein to cytochrome c. Cytochrome c1 is present at reduced levels in the skeletal muscle and skin fibroblasts of affected individuals. Moreover, studies on yeast mutants and affected individuals' fibroblasts have shown that exogenous expression of wild-type CYC1 rescues complex III activity, demonstrating the deleterious effect of each mutation on cytochrome c1 stability and complex III activity.
许多线粒体呼吸链复合物 III 结构异常的个体在基因上仍未被定义。在这里，我们报告了两个无关的儿童中 CYC1 （编码复合物 III 的细胞色素 c1 亚基）的突变（c.288G>T [p.Trp96Cys]和 c.643C>T [p.Leu215Phe]），这些儿童反复出现酮症酸中毒和胰岛素反应性高血糖。细胞色素 c1 是复合物 III 的含铁血红素成分，介导电子从 Rieske 铁硫蛋白向细胞色素 c 的转移。受影响个体的骨骼肌和皮肤成纤维细胞中细胞色素 c1 的水平降低。此外，对酵母突变体和受影响个体的成纤维细胞的研究表明，外源性表达野生型 CYC1 可恢复复合物 III 的活性，表明每个突变对细胞色素 c1 稳定性和复合物 III 活性的有害影响。
