Human mitochondrial complex I assembly is mediated by NDUFAF1
Open Access
- 7 October 2005
- journal article
- Published by Wiley in The FEBS Journal
- Vol. 272 (20), 5317-5326
- https://doi.org/10.1111/j.1742-4658.2005.04928.x
Abstract
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.Keywords
This publication has 18 references indexed in Scilit:
- Human mitochondrial complex I assembles through the combination of evolutionary conserved modules: a framework to interpret complex I deficienciesHuman Molecular Genetics, 2004
- Development and Characterization of a Conditional Mitochondrial Complex I Assembly SystemJournal of Biological Chemistry, 2004
- Assembly of Respiratory Complexes I, III, and IV into NADH Oxidase Supercomplex Stabilizes Complex I in Paracoccus denitrificansPublished by Elsevier ,2004
- Identification and Characterization of a Common Set of Complex I Assembly Intermediates in Mitochondria from Patients with Complex I DeficiencyJournal of Biological Chemistry, 2003
- Analysis of the Subunit Composition of Complex I from Bovine Heart Mitochondria*SMolecular & Cellular Proteomics, 2003
- Impact of Mutations Affecting ND Mitochondria-encoded Subunits on the Activity and Assembly of Complex I in Chlamydomonas. Implication for the Structural Organization of the EnzymeJournal of Molecular Biology, 2002
- Blue Native electrophoresis to study mitochondrial and other protein complexesMethods, 2002
- CIA30 complex I assembly factor: a candidate for human complex I deficiency?Human Genetics, 2002
- Structure of the respiratory NADH:ubiquinone oxidoreductase (complex I)Current Opinion in Structural Biology, 1999
- Involvement of two novel chaperones in the assembly of mitochondrial NADH:ubiquinone oxidoreductase (complex I)Journal of Molecular Biology, 1998