Congenital deficiency of two polypeptide subunits of the iron-protein fragment of mitochondrial complex I.
Congenital deficiency of two polypeptide subunits of the iron-protein fragment of mitochondrial complex I.
复制标题
先天性缺乏线粒体复合物 I 铁蛋白片段的两个多肽亚基。
DOI：
10.1172/jci112834
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Lehninger,AL
中科院分区：
文献类型：
--
作者：
Moreadith,RW;Cleeter,MW;Ragan,CI;Batshaw,ML;Lehninger,AL
最近，我们报告了一例由于先天性复合体I （nadh -泛醌氧化还原酶）缺乏而导致的严重乳酸酸中毒。我们现在报告进一步的酶和免疫特性。NADH和铁氰化物复合物I活性的滴定（以NADH-铁氰化物还原酶测量）在患者组织的线粒体中明显改变。此外，复合物I的抗血清免疫沉淀nadh -铁氰化物还原酶来自对照组，而不是患者的线粒体。然而，复合物I多肽的免疫沉淀和十二烷基硫酸钠-聚丙烯酰胺凝胶电泳表明，构成复合物I的25个多肽中的大多数存在于受影响的线粒体中。使用亚单位选择性抗血清对复合物I的铁蛋白片段的主要多肽进行更详细的分析，发现75-和13-kD多肽的选择性缺失。这些发现表明，该患者疾病的潜在基础是先天缺乏至少两种包含复合物I的铁蛋白片段的多肽，这导致无法正确组装功能性酶复合物。图片
Recently, we described a patient with severe lactic acidosis due to congenital complex I (NADH-ubiquinone oxidoreductase) deficiency. We now report further enzymatic and immunological characterizations. Both NADH and ferricyanide titrations of complex I activity (measured as NADH-ferricyanide reductase) were distinctly altered in the mitochondria from the patient's tissues. In addition, antisera against complex I immunoprecipitated NADH-ferricyanide reductase from the control but not the patient's mitochondria. However, immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of complex I polypeptides demonstrated that the majority of the 25 polypeptides comprising complex I were present in the affected mitochondria. A more detailed analysis using subunit selective antisera against the main polypeptides of the iron-protein fragments of complex I revealed a selective absence of the 75- and 13-kD polypeptides. These findings suggest that the underlying basis for this patient's disease was a congenital deficiency of at least two polypeptides comprising the iron-protein fragment of complex I, which resulted in the inability to correctly assemble a functional enzyme complex.Images