Assembly Factors of Human Mitochondrial Respiratory Chain Complexes: Physiology and Pathophysiology
Assembly Factors of Human Mitochondrial Respiratory Chain Complexes: Physiology and Pathophysiology
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DOI：
10.1007/978-1-4614-3573-0_4
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发表时间：
2012-01-01
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影响因子：
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通讯作者：
Zeviani, Massimo
中科院分区：
文献类型：
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作者：
Ghezzi, Daniele;Zeviani, Massimo
线粒体疾病是与氧化磷酸化 (OXPHOS) 系统异常相关的临床综合征，该系统主要负责细胞中能量的产生。 OXPHOS 由线粒体呼吸链 (MRC) 的五种酶复合物在线粒体内膜中进行。构成这些多聚体复合物的亚基具有双重遗传起源：线粒体或细胞核。因此，线粒体综合征可能是由于线粒体 DNA 突变或核基因异常所致。 MRC 复合物的生物发生是一个复杂且精细调整的过程。最近发现的几种与 OXPHOS 相关的人类基因在不同的临床综合征中发生突变，表明大多数遗传性线粒体疾病是由核基因引起的，其中许多基因编码 MRC 复合物正确组装/稳定所必需的蛋白质。这些过程的详细机制尚未完全了解，许多此类因子的确切功能仍然不清楚。我们对不同 MRC 复合物的假设组装过程进行了概述，重点关注已知的组装因子及其临床重要性。
Mitochondrial disorders are clinical syndromes associated with abnormalities of the oxidative phosphorylation (OXPHOS) system, the main responsible for the production of energy in the cell. OXPHOS is carried out in the inner mitochondrial membrane by the five enzymatic complexes of the mitochondrial respiratory chain (MRC). The subunits constituting these multimeric complexes have a dual genetic origin, mitochondrial or nuclear. Hence, mitochondrial syndromes can be due to mutations of mitochondrial DNA or to abnormalities in nuclear genes. The biogenesis of the MRC complexes is an intricate and finely tuned process. The recent discovery of several OXPHOS-related human genes, mutated in different clinical syndromes, indicates that the majority of the inherited mitochondrial disorders are due to nuclear genes, and many of them encode proteins necessary for the proper assembly/stability of the MRC complexes. The detailed mechanisms of these processes are not fully understood and the exact function of many such factors remains obscure.We present an overview on the hypothesized assembly processes of the different MRC complexes, focusing on known assembly factors and their clinical importance.