Complex I and the cAMP cascade in human physiopathology.
A cAMP-dependent protein kinase (PKA) is localized in mammalian mitochondria with the catalytic site at the matrix side of the membrane where it phosphorylates a number of proteins. One of these is the 18 kDa(IP) subunit of the mammalian complex I of the respiratory chain, encoded by the nuclear NDUFS4 gene. Mitochondria have a Ca(2+)-inhibited phosphatase, which dephosphorylates the 18 kDa phosphoprotein of complex I. In fibroblast and myoblast cultures cAMP-dependent phosphorylation of the 18 kDa protein is associated with stimulation of complex I and overall respiratory activity with NAD-linked substrates. Mutations in the human NDUFS4 gene have been found, which in the homozygous state are associated with deficiency of complex I and fatal neurological syndrome.
Papa
S
S
Department of Medical Biochemistry and Biology, University of Bari, Italy. papabchm@cimedoc.uniba.it
Scacco
S
S
Sardanelli
A M
AM
Petruzzella
V
V
Vergari
R
R
Signorile
A
A
Technikova-Dobrova
Z
Z
D001483:Base Sequence; D000242:Cyclic AMP / Q000378:metabolism*; D042967:Electron Transport Complex I; D006801:Humans; D028361:Mitochondrial Diseases / Q000378:metabolism* / Q000503:physiopathology*; D008969:Molecular Sequence Data; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D000242:Cyclic AMP; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I