|Title||Human mitochondrial complex I assembly is mediated by NDUFAF1.|
|Publication Type||Journal Article|
|Year of Publication||2005|
|Authors||Vogel, RO, Janssen, RJRJ, Ugalde, C, Grovenstein, M, Huijbens, RJ, Visch, H-J, van den Heuvel, LP, Willems, PH, Zeviani, M, Smeitink, JAM, Nijtmans, LGJ|
|Date Published||2005 Oct|
|Keywords||Cell Fractionation, Cell Line, Doxycycline, Electron Transport Complex I, Electron Transport Complex IV, HeLa Cells, Humans, Membrane Proteins, Microscopy, Fluorescence, Mitochondria, Mitochondrial Diseases, Mitochondrial Proteins, Mutation, NAD(P)H Dehydrogenase (Quinone), NADH Dehydrogenase, Protein Subunits, Protein Transport, RNA, Small Interfering, Transfection|
Complex I (NADH:ubiquinone oxidoreductase) is the largest multiprotein enzyme of the oxidative phosphorylation system. Its assembly in human cells is poorly understood and no proteins assisting this process have yet been described. A good candidate is NDUFAF1, the human homologue of Neurospora crassa complex I chaperone CIA30. Here, we demonstrate that NDUFAF1 is a mitochondrial protein that is involved in the complex I assembly process. Modulating the intramitochondrial amount of NDUFAF1 by knocking down its expression using RNA interference leads to a reduced amount and activity of complex I. NDUFAF1 is associated to two complexes of 600 and 700 kDa in size of which the relative distribution is altered in two complex I deficient patients. Analysis of NDUFAF1 expression in a conditional complex I assembly system shows that the 700 kDa complex may represent a key step in the complex I assembly process. Based on these data, we propose that NDUFAF1 is an important protein for the assembly/stability of complex I.
|Alternate Journal||FEBS J.|