Human mitochondrial complex I assembly is mediated by NDUFAF1 |
| |
Authors: | Vogel Rutger O Janssen Rolf J R J Ugalde Cristina Grovenstein Melissa Huijbens Richard J Visch Henk-Jan van den Heuvel Lambert P Willems Peter H Zeviani Massimo Smeitink Jan A M Nijtmans Leo G J |
| |
Institution: | Department of Paediatrics, Radboud University Nijmegen Medical Centre, Netherlands. |
| |
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: | |
本文献已被 PubMed 等数据库收录! |
|