Article
- The EMBO Journal (2008) 27, 1736 - 1746
- doi:10.1038/emboj.2008.98
Published online: 22 May 2008
Subject Category:
The iron–sulphur protein Ind1 is required for effective complex I assembly
Katrine Bych1,a, Stefan Kerscher2,a, Daili J A Netz3,a, Antonio J Pierik3, Klaus Zwicker2, Martijn A Huynen4, Roland Lill3, Ulrich Brandt2 and Janneke Balk1
- Department of Plant Sciences, University of Cambridge, Cambridge, UK
- Fachbereich Medizin, Zentrum der Biologischen Chemie, Molekulare Bioenergetik, Centre of Excellence Frankfurt 'Macromolecular Complexes', Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany
- Institut für Zytobiologie, Philipps-Universität Marburg, Marburg, Germany
- Centre for Molecular and Biomolecular Informatics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Correspondence to:
Janneke Balk, Department of Plant Sciences, University of Cambridge, Downing Street, Cambridge CB2 3EA, UK. Tel.: +44 1223 330225; Fax: +44 1223 333953; E-mail: jb511@cam.ac.uk
aThese authors contributed equally to this work
Received 5 March 2008; Accepted 28 April 2008
Abstract
NADH:ubiquinone oxidoreductase (complex I) of the mitochondrial inner membrane is a multi-subunit protein complex containing eight iron–sulphur (Fe–S) clusters. Little is known about the assembly of complex I and its Fe–S clusters. Here, we report the identification of a mitochondrial protein with a nucleotide-binding domain, named Ind1, that is required specifically for the effective assembly of complex I. Deletion of the IND1 open reading frame in the yeast Yarrowia lipolytica carrying an internal alternative NADH dehydrogenase resulted in slower growth and strongly decreased complex I activity, whereas the activities of other mitochondrial Fe–S enzymes, including aconitase and succinate dehydrogenase, were not affected. Two-dimensional gel electrophoresis, in vitro activity tests and electron paramagnetic resonance signals of Fe–S clusters showed that only a minor fraction (
20%) of complex I was assembled in the ind1 deletion mutant. Using in vivo and in vitro approaches, we found that Ind1 can bind a [4Fe–4S] cluster that was readily transferred to an acceptor Fe–S protein. Our data suggest that Ind1 facilitates the assembly of Fe–S cofactors and subunits of complex I.
Keywords:
- metal cofactor,
- mitochondria,
- myopathy,
- NTPase,
- oxidoreductase
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