Scacco Salvatore, Petruzzella Vittoria, Bertini Enrico, Luso Arcangela, Papa Francesco, Bellomo Francesco, Signorile Anna, Torraco Alessandra, Papa Sergio
Department of Medical Biochemistry, Biology and Physics, University of Bari, Italy.
Ital J Biochem. 2006 Sep-Dec;55(3-4):254-62.
This paper summarizes observations on the genetic and biochemical basis of hereditary defects of complex I (NADH-ubiquinone oxidoreductase) of the respiratory chain in human neurological patients. Two different types of functional defects of the complex are described. In one type mutations in the NDUFS1 and NDUFS4 nuclear structural genes of the complex were identified in two unrelated families. Both NDUFS1 and NDUFS4 neurological disorders were transmitted by autosomic recessive inheritance. The two mutations resulted in different impact on cellular metabolism. The NDUFS4 mutation, giving a more severe, fatal pathological pattern, resulted in a defective assembly of the complex and complete suppression of the enzymatic activity. The NDUFS1 mutation, with less severe progressive pathology, caused only partial inhibition of the complex but enhanced production of oxygen free radicals. In the second type of deficiencies extensive mutational analysis did not reveal pathogenic mutations in complex I genes but a decline in the level and activity of complex I, III, and IV were found, apparently associated with alteration in the cardiolipin membrane distribution.
本文总结了对人类神经疾病患者呼吸链复合体I（NADH-泛醌氧化还原酶）遗传性缺陷的遗传和生化基础的观察结果。描述了该复合体两种不同类型的功能缺陷。在一种类型中，在两个不相关的家族中鉴定出该复合体的NDUFS1和NDUFS4核结构基因中的突变。NDUFS1和NDUFS4神经疾病均通过常染色体隐性遗传传递。这两种突变对细胞代谢产生了不同的影响。NDUFS4突变导致更严重的致命病理模式，导致复合体组装缺陷并完全抑制酶活性。NDUFS1突变具有较轻的进行性病理，仅引起复合体的部分抑制，但增加了氧自由基的产生。在第二种缺陷类型中，广泛的突变分析未发现复合体I基因中的致病突变，但发现复合体I、III和IV的水平和活性下降，这显然与心磷脂膜分布的改变有关。
