cAMP-dependent phosphorylation of the nuclear encoded 18-kDa (IP) subunit of respiratory complex I and activation of the complex in serum-starved mouse fibroblast cultures

A study is presented on the in vivo effect of elevated cAMP levels induced by cholera toxin on the phosphorylation of subunits of the mitochondrial re spiratory complexes and their activities in Balb/c 3T3 mouse fibroblast cul tures. Treatment of serum-starved fibroblasts with cholera toxin promoted s erine phosphorylation in the 18-kDa subunit of complex I. Phosphorylation o f the 18-kDa subunit, in response to cholera toxin treatment of fibroblasts , was accompanied by a 2-3-fold enhancement of the rotenone-sensitive endog enous respiration of fibroblasts, of the rotenone-sensitive NADH oxidase, a nd of the NADH:ubiquinone oxidoreductase activity of complex I. Direct expo sure of fibroblasts to dibutyryl cAMP resulted in an equally potent stimula tion of the NADH:ubiquinone oxidoreductase activity. Stimulation of complex I activity and respiration with NAD-linked substrates were also observed u pon short incubation of isolated fibroblast mitoplasts with dibutyryl cAMP and ATP, which also promoted phosphorylation of the 18-kDa subunit. These o bservations document an extension of cAMP-mediated intracellular signal tra nsduction to the regulation of cellular respiration.