Defects in the biosynthesis of mitochondrial heme c and heme a in yeast and mammals
Defects in the biosynthesis of mitochondrial heme c and heme a in yeast and mammals
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DOI：
10.1016/j.bbabio.2004.09.002
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发表时间：
2004-12-06
影响因子：
4.3
通讯作者：
Barrientos, A
中科院分区：
文献类型：
--
作者：
Moraes, CT;Diaz, F;Barrientos, A
血红素生物合成的缺陷与大量疾病有关，但大多数在卟啉症中被认识到，卟啉症是由生物合成中间体的积累引起的神经内脏或皮肤疾病。然而，作为氧化磷酸化系统的一部分的血红素组的成熟缺陷现在也被认为是疾病的重要原因。电子传递链含有a、B和c型血红素基团，所有这些基团都直接参与电子传递反应。在这篇文章中，我们回顾了酵母和人类中血红素a（细胞色素c氧化酶的辅基）和血红素c（细胞色素c的辅基）成熟所涉及的酶突变的影响。COX10和COX15是最初在酿酒酵母中鉴定的两个基因，已发现它们导致人类婴儿细胞色素e氧化酶缺乏症。它们参与血红素B的法尼基化和羟基化，这是形成血红素a所必需的步骤，血红素a是细胞色素氧化酶组装和活性所需的辅基。单个等位基因中细胞色素c血红素裂解酶基因的缺失也与人类疾病相关，称为小眼伴线状皮肤缺损（MLS）综合征。细胞色素c血红素裂解酶是将血红素基团共价连接到脱辅基细胞色素c多肽所必需的。重现这些疾病的小鼠模型的产生为临床综合征的发病机制提供了新的信息。(C)2004年由Elsevier B.V.出版
Defects in heme biosynthesis have been associated with a large number of diseases, but mostly recognized in porphyrias, which are neurovisceral or cutaneous disorders caused by the accumulation of biosynthetic intermediates. However, defects in the maturation of heme groups that are part of the oxidative phosphorylation system are now also recognized as important causes of disease. The electron transport chain contains heme groups of the types a, b and c, all of which are directly involved in electron transfer reactions. In this article, we review the effect of mutations in enzymes involved in the maturation of heme a (the prosthetic group of cytochrome c oxidase) and heme c (the prosthetic group of cytochrome c) both in yeast and in humans. COX10 and COX15 are two genes, initially identified in Saccharomyces cerevisiae that have been found to cause infantile cytochrome e oxidase deficiency in humans. They participate in the farnesylation and hydroxylation of heme b, steps that are necessary for the formation of heme a, the prosthetic group required for cytochrome oxidase assembly and activity. Deletion of the cytochrome c heme lyase gene in a single allele has also been associated with a human disease, known as Microphthalmia with Linear Skin defects (MLS) syndrome. The cytochrome c heme lyase is necessary to covalently attach the heme group to the apocytochrome c polypeptide. The production of mouse models recapitulating these diseases is providing novel information on the pathogenesis of clinical syndromes. (C) 2004 Published by Elsevier B.V.