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

Scacco, Salvatore; Vergari, Rosaria; Scarpulla, Richard C.; Technikova-Dobrova, Zuzana; Sardanelli, Anna Maria; Lambo, Rossana; Lorusso, Vito; Papa, Sergio

doi:10.1074/jbc.m001174200

Cited by 117 publications

(99 citation statements)

References 33 publications

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“…Further conditions are specified in the legends to figures. Fibroblasts harvested and mitoplast preparation as described in [20].…”

Section: Cell Culture and Mitoplast Preparationmentioning

confidence: 99%

“…Mitoplasts were exposed to ultrasound energy for 15 s at 0°C and the V max of NADH-UQ oxidoreductase activity was measured as described in [20]. Cytochrome c oxidase activity was measured as in [20].…”

Section: Complex I and Complex Iv Assaymentioning

confidence: 99%

“…The cAMP effects can be directly associated with phosphorylation of complex I subunits [9,[20][21][22] and or PKA-mediated changes in the redox [23]/nitrosylation [24] state of complex I subunits.…”

Section: Serum-limitation-induced Ros Production Is Not Associatedmentioning

confidence: 99%

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cAMP controls oxygen metabolism in mammalian cells

et al. 2006

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The impact of cAMP on ROS-balance in human and mammalian cell cultures was studied. cAMP reduced accumulation of ROS induced by serum-limitation, under conditions in which there was no significant change in the activity of scavenger systems. This effect was associated with cAMP-dependent activation of the NADH-ubiquinone oxidoreductase activity of complex I. In fibroblasts from a patient a genetic defect in the 75 kDa FeS-protein subunit of complex I resulted in inhibition of the activity of the complex and enhanced ROS production, which were reversed by cAMP. A missense genetic defect in the NDUFS4 subunit, putative substrate of PKA, suppressed, on the other hand, the activity of the complex and prevented ROS production.

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“…Further conditions are specified in the legends to figures. Fibroblasts harvested and mitoplast preparation as described in [20].…”

Section: Cell Culture and Mitoplast Preparationmentioning

confidence: 99%

Section: Complex I and Complex Iv Assaymentioning

confidence: 99%

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cAMP controls oxygen metabolism in mammalian cells

et al. 2006

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“…The question is therefore raised as to the physiological meaning of such multiple binding and regulating sites for adenylic nucleotides in the control and regulation of cellular energy metabolism. Extrapolation of previous ndings to the in vivo situation is complicated because the cellular respiration is a function of: a) the electron supply to the respiratory chain, sustained by dehydrogenase activity and intermediate metabolism, b) ATP turnover, c) the magnitude of the proton leak and the stoichiometry of the different proton pumps and, d) signal transduction pathways, for example, phosphorylations of respiratory chain complexes (54,55). Indeed, during oxidative phosphorylation, intracellular adenylic nucleotides could play a key role at two levels, that is, as components of the free energy of the ATP synthesis (i.e., phosphate potential) and as kinetic effectors of the COX.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Cytochrome c Oxidase by Adenylic Nucleotides. Is Oxidative Phosphorylation Feedback Regulated by its End‐Products?

Beauvoit¹,

Rigoulet²

2001

IUBMB Life

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SummaryCytochrome c oxidase, which catalyzes an irreversible step of the respiratory chain, is one of the rate-controlling steps of oxidative phosphorylation on isolated mitochondria. The rate of electron transfer through the complex is primarily controlled by the associated thermodynamic forces, i.e., the span in redox potential between oxygen and cytochrome c and the protonmotive force. However, the electron ux also depends on the various kinetic effectors, including adenylic nucleotides. Although the number of binding sites for ATP and ADP on cytochrome oxidase is still a matter of debate, experiments performed on the solubilized and reconstituted enzyme provide strong functional evidence that the mammalian cytochrome c oxidase binds adenylic nucleotides on both sides of the inner membrane. These effects include modi cation in cytochrome c af nity, allosteric inhibition and changes in proton pumping ef ciency. Immunological studies have pointed out the role of subunit IV and that of an ATP-binding protein, subunit VIa, in these kinetic regulations. In yeast, the role of the nuclear-encoded subunits in assembly and regulation of the cytochrome c oxidase has been further substantiated by using gene-disruption analysis. Using a subunit VIa-null mutant, the consequences of the ATP regulation on oxidative phosphorylation have been further investigated on isolated mitochondria. Taken together, the data demonstrate that there are multiple regulating sites for ATP on the yeast cytochrome oxidase with respect to the location (matrix versus cytosolic side), kinetic effect (activation versus inhibition) and consequence on the ow-force relationships. The question is therefore raised as to the

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“…In vitro phosphorylation of complex I with added ATP has been performed in a number of works to find potential substrates of mitochondrial kinases in particular protein kinase A (PKA) (6 -10) and pyruvate dehydrogenase kinase (11,12). In human (13) and mammalian cell cultures (7,14) cAMP-dependent in vitro phosphorylation of complex I subunits has been demonstrated and was associated with stimulation of the NADH:ubiquinone oxidoreductase activity of the complex. cAMP has also been found to reduce accumulation of oxygen free radicals from human and murine cells in culture (15,16).…”

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confidence: 99%