Congenital deficiency of two polypeptide subunits of the iron-protein fragment of mitochondrial complex I.
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.
D006801:Humans; D007501:Iron / Q000032:analysis; D007700:Kinetics; D046911:Macromolecular Substances; D008929:Mitochondria, Heart / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology*; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D012016:Reference Values; D013367:Submitochondrial Particles / Q000201:enzymology
D046911:Macromolecular Substances; D007501:Iron; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases