Mutation in the NDUFS4 gene of complex I abolishes cAMP-dependent activation of the complex in a child with fatal neurological syndrome.
Evidence is presented showing that in a patient with fatal neurological syndrome, the homozygous 5 bp duplication in the cDNA of the NDUFS4 18 kDa subunit of complex I abolishes cAMP-dependent phosphorylation of this protein and activation of the complex. These findings show for the first time that human complex I is regulated via phosphorylation of the subunit encoded by the NDUFS4 gene.
Papa
S
S
Department of Medical Biochemistry and Biology, University of Bari, Italy. papabchm@cimedoc.uniba.it
Scacco
S
S
Sardanelli
A M
AM
Vergari
R
R
Papa
F
F
Budde
S
S
van den Heuvel
L
L
Smeitink
J
J
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D042967:Electron Transport Complex I; D004789:Enzyme Activation; D017809:Fatal Outcome; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007223:Infant; D007888:Leigh Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009247:NADH, NADPH Oxidoreductases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D021122:Protein Subunits; D017386:Sequence Homology, Amino Acid
D021122:Protein Subunits; D000242:Cyclic AMP; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I