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.
Original language | English |
---|---|
Pages (from-to) | 5317-5326 |
Number of pages | 10 |
Journal | FEBS Journal |
Volume | 272 |
Issue number | 20 |
DOIs | |
Publication status | Published - Oct 2005 |
Keywords
- Assembly
- Complex I
- Mitochondria
- NDUFAF1
- Oxidative phosphorylation
ASJC Scopus subject areas
- Biochemistry