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

doi:10.1111/j.1742-4658.2005.04928.x

Human mitochondrial complex I assembly is mediated by NDUFAF1

FEBS J. 2005 Oct;272(20):5317-26. doi: 10.1111/j.1742-4658.2005.04928.x.

Authors

Rutger O Vogel¹, 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

Affiliation

¹ Department of Paediatrics, Radboud University Nijmegen Medical Centre, Netherlands.

PMID: 16218961
DOI: 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Fractionation
Cell Line
Doxycycline / pharmacology
Electron Transport Complex I / biosynthesis*
Electron Transport Complex I / deficiency
Electron Transport Complex I / genetics
Electron Transport Complex I / metabolism
Electron Transport Complex IV / metabolism
HeLa Cells
Humans
Membrane Proteins / genetics
Membrane Proteins / metabolism
Membrane Proteins / physiology*
Microscopy, Fluorescence
Mitochondria / drug effects
Mitochondria / metabolism
Mitochondrial Diseases / metabolism
Mitochondrial Proteins / genetics
Mitochondrial Proteins / metabolism*
Mitochondrial Proteins / physiology
Mutation / genetics
NAD(P)H Dehydrogenase (Quinone) / genetics
NADH Dehydrogenase
Protein Subunits / metabolism
Protein Transport / physiology
RNA, Small Interfering / genetics
Transfection

Substances

Membrane Proteins
Mitochondrial Proteins
NDUFS8 protein, human
Protein Subunits
RNA, Small Interfering
NAD(P)H Dehydrogenase (Quinone)
MT-ND5 protein, human
NADH Dehydrogenase
cytochrome C oxidase subunit II
Electron Transport Complex IV
Electron Transport Complex I
NDUFAF1 protein, human
Doxycycline