Mammalian complex I: a regulable and vulnerable pacemaker in mitochondrial respiratory function

Biochim Biophys Acta. 2008 Jul-Aug;1777(7-8):719-28. doi: 10.1016/j.bbabio.2008.04.005. Epub 2008 Apr 11.


In this paper the regulatory features of complex I of mammalian and human mitochondria are reviewed. In a variety of mitotic cell-line cultures, activation in vivo of the cAMP cascade, or direct addition of cAMP, promotes the NADH-ubiquinone oxidoreductase activity of complex I and lower the cellular level of ROS. These effects of cAMP are found to be associated with PKA-mediated serine phosphorylation in the conserved C-terminus of the subunit of complex I encoded by the nuclear gene NDUFS4. PKA mediated phosphorylation of this Ser in the C-terminus of the protein promotes its mitochondrial import and maturation. Mass-spectrometry analysis of the phosphorylation pattern of complex I subunits is also reviewed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Conserved Sequence
  • Cyclic AMP / metabolism
  • Electron Transport Complex I / chemistry
  • Electron Transport Complex I / metabolism*
  • Homeostasis
  • Kinetics
  • Mammals
  • Mitochondria / enzymology*
  • Models, Molecular
  • Molecular Sequence Data
  • Oxygen Consumption*
  • Sequence Homology, Amino Acid


  • Cyclic AMP
  • Electron Transport Complex I