Mutations in CYC1, Encoding Cytochrome c₁ Subunit of Respiratory Chain Complex III, Cause Insulin-Responsive Hyperglycemia

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• 作者：Pauline Gaignard ; Minal Menezes ; Manuel Schiff ; Aur¨¦lien Bayot ; Malgorzata Rak ; H¨¦l¨¨ne Ogier?de?Baulny ; Chen-Hsien Su ; Mylene Gilleron ; Anne Lombes ; Heni Abida ; Alex ; er Tzagoloff ; Lisa Riley ; S ; ra?T. Cooper ; Kym Mina ; Padma Sivadorai ; Mark?R. Davis ; Richard?J.N. Allcock ; Nina Kresoje ; Nigel?G. Laing ; David?R. Thorburn ; et al.
• 刊名：The American Journal of Human Genetics
• 出版年：2013
• 出版时间：8 August, 2013
• 年：2013
• 卷：93
• 期：2
• 页码：384-389
• 全文大小：1076 K

文摘

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.