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

Abstract:

: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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Vogel RO,Janssen RJ,van den Brand MA,Dieteren CE,Verkaart S,Koopman WJ,Willems PH,Pluk W,van den Heuvel LP,Smeitink JA,Nijtmans LG

doi

10.1101/gad.408407

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

615-24

issue

5

eissn

0890-9369

issn

1549-5477

pii

21/5/615

journal_volume

21

pub_type

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