Mitochondrial cytochrome c oxidase deficiency.
Mitochondrial cytochrome c oxidase deficiency.
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DOI：
10.1042/cs20150707
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发表时间：
2016-03
期刊：
影响因子：
--
通讯作者：
Rustin P
中科院分区：
文献类型：
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作者：
Rak M;Bénit P;Chrétien D;Bouchereau J;Schiff M;El-Khoury R;Tzagoloff A;Rustin P
与其他线粒体呼吸链成分一样，在细胞色素c氧化酶缺乏症患者中观察到显著的临床和遗传异质性。这构成了一个相当大的诊断挑战，并提出了一些令人困惑的问题。到目前为止，已经报道了线粒体和核DNA中30多个基因的病理性突变，影响了酶的结构亚基或参与其生物发生的蛋白质。在这篇综述中，我们讨论了细胞色素氧化酶缺乏症的分子基础的鉴定和缺乏任何有效的治疗方法所造成的疾病，这种缺陷的壮观的进展之间的差异的可能原因。这带来了许多未解决的问题，涉及临床表现的频繁延迟，可变的过程和严重程度，以及组织参与往往与这些疾病。在这种情况下，我们强调研究这些疾病的不同模型的重要性，但也讨论了在大多数可用的疾病模型中遇到的局限性。在未来，除了使用基因、细胞或器官的替代疗法之外，可能需要更好地了解这些线粒体疾病的潜在机制，以开发有效的治疗方法。
As with other mitochondrial respiratory chain components, marked clinical and genetic heterogeneity is observed in patients with a cytochrome c oxidase deficiency. This constitutes a considerable diagnostic challenge and raises a number of puzzling questions. So far, pathological mutations have been reported in more than 30 genes, in both mitochondrial and nuclear DNA, affecting either structural subunits of the enzyme or proteins involved in its biogenesis. In this review, we discuss the possible causes of the discrepancy between the spectacular advances made in the identification of the molecular bases of cytochrome oxidase deficiency and the lack of any efficient treatment in diseases resulting from such deficiencies. This brings back many unsolved questions related to the frequent delay of clinical manifestation, variable course and severity, and tissue-involvement often associated with these diseases. In this context, we stress the importance to study different models of these diseases, but also discuss the limitations encountered in most available disease models. In the future, with the possible exception of replacement therapy using genes, cells or organs, a better understanding of underlying mechanism(s) of these mitochondrial diseases is presumably required to develop efficient therapy.