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.
Vogel
Rutger O
RO
Department of Paediatrics, Nijmegen Centre for Mitochondrial Disorders, Radboud University Nijmegen Medical Centre, Nijmegen 6500 HB, The Netherlands.
Janssen
Rolf J R J
RJ
van den Brand
Mariël A M
MA
Dieteren
Cindy E J
CE
Verkaart
Sjoerd
S
Koopman
Werner J H
WJ
Willems
Peter H G M
PH
Pluk
Wendy
W
van den Heuvel
Lambert P W J
LP
Smeitink
Jan A M
JA
Nijtmans
Leo G J
LG
D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D002460:Cell Line; D042967:Electron Transport Complex I / Q000378:metabolism*; D047108:Embryonic Development; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009245:NADH Dehydrogenase / Q000032:analysis / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D034622:RNA Interference
D048868:Adaptor Proteins, Signal Transducing; C518657:Ecsit protein, human; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I; C506342:NDUFAF1 protein, human