Human mitochondrial complex I assembly is mediated by NDUFAF1

Rutger O. Vogel, Rolf J R J Janssen, Cristina Ugalde, Melissa Grovenstein, Richard J. Huijbens, Henk Jan Visch, Lambert P. Van Den Heuvel, Peter H. Willems, Massimo Zeviani, Jan A M Smeitink, Leo G J Nijtmans

Research output: Contribution to journalArticlepeer-review


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 languageEnglish
Pages (from-to)5317-5326
Number of pages10
JournalFEBS Journal
Issue number20
Publication statusPublished - Oct 2005


  • Assembly
  • Complex I
  • Mitochondria
  • Oxidative phosphorylation

ASJC Scopus subject areas

  • Biochemistry


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