Cytosolic signaling protein Ecsit also localizes to mitochondria where it interacts with chaperone NDUFAF1 and functions in complex I assembly

Ecsit is a cytosolic adaptor protein essential for inflammatory response and embryonic development via the Toll-like and BMP (bone morphogenetic protein) signal transduction pathways, respectively. Here, we demonstrate a mitochondrial function for Ecsit (an evolutionary conserved signaling intermediate in Toll pathways) in the assembly of mitochondrial complex I (NADH:ubiquinone oxidoreductase). An N-terminal targeting signal directs Ecsit to mitochondria, where it interacts with assembly chaperone NDUFAF1 in 500- to 850-kDa complexes as demonstrated by affinity purification and vice versa RNA interference (RNAi) knockdowns. In addition, Ecsit knockdown results in severely impaired complex I assembly and disturbed mitochondrial function. These findings support a function for Ecsit in the assembly or stability of mitochondrial complex I, possibly linking assembly of oxidative phosphorylation complexes to inflammatory response and embryonic development.

Bibliographic Details

Main Authors:	Vogel, Rutger O., Janssen, Rolf J.R.J., Van Den Brand, Mariël A.M., Dieteren, Cindy E.J., Verkaart, Sjoerd, Koopman, Werner J.H., Willems, Peter H.G.M., Pluk, Wendy, Van Den Heuvel, Lambert P.W.J., Smeitink, Jan A.M., Nijtmans, Leo G.J.
Format:	Article/Letter to editor biblioteca
Language:	English
Subjects:	Complex I, Ecsit, Mitochondria, NADH:ubiquinone oxidoreductase, NDUFAF1, Oxidative phosphorylation,
Online Access:	https://research.wur.nl/en/publications/cytosolic-signaling-protein-ecsit-also-localizes-to-mitochondria-
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