Novel function of the regulatory subunit of protein kinase A: regulation of cytochrome c oxidase activity and cytochrome c release

Biochemistry. 1998 Oct 6;37(40):14175-80. doi: 10.1021/bi981402a.


There have been speculations that the regulatory (R) subunit of the cAMP-dependent protein kinase (PKA) may have other functions. A recent study has shown that the catalytic (C) subunit of PKA may be regulated in a cAMP- and R subunit-independent manner. However, evidence linking a function to the R subunit apart from inhibiting the C subunit has been elusive. In this report, interaction cloning experiments showed that the RIalpha subunit association with the cytochrome c oxidase subunit Vb (CoxVb) is cAMP-sensitive. Interaction was detected with a GST-RIalpha fusion protein as well as by coimmunoprecipitation. Transient treatment with cAMP-elevating agents inhibited cytochrome c oxidase in Chinese hamster ovary (CHO) cells with a concomitant decrease in cytochrome c levels in the mitochondria and an increase in its release into the cytosol. Furthermore, mutant cells harboring a defective RIalpha show increased cytochrome c oxidase activity and also constitutively lower levels of cytochrome c in comparison to either the wild-type cells or the C subunit mutant. These results suggest a novel mechanism of cAMP signaling through the interaction of RIalpha with CoxVb thereby regulating cytochrome c oxidase activity as well as the cytochrome c levels.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CHO Cells
  • Cloning, Molecular
  • Cricetinae
  • Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cyclic AMP-Dependent Protein Kinases / physiology*
  • Cytochrome c Group / metabolism*
  • Electron Transport Complex IV / metabolism*
  • Gene Deletion
  • Glutathione Transferase / genetics
  • Mice
  • Mitochondria / enzymology
  • Precipitin Tests
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Signal Transduction / genetics
  • Subcellular Fractions / enzymology


  • Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
  • Cytochrome c Group
  • Prkar1a protein, mouse
  • Recombinant Fusion Proteins
  • Electron Transport Complex IV
  • Glutathione Transferase
  • Cyclic AMP-Dependent Protein Kinases