Reductive nitrosylation of the cardiolipin-ferric cytochrome c complex

IUBMB Life. 2014 Jun;66(6):438-47. doi: 10.1002/iub.1283. Epub 2014 Jun 30.

Abstract

Native horse heart cytochrome c (cytc) displays a very low reactivity toward ligands and does not exhibit catalytic properties. However, upon bovine cardiolipin (CL) binding, cytc achieves myoglobin-like properties. Here, NO binding to CL-cytc(III) between pH 7.2 and 9.5, at 20 °C, is reported. At pH 7.2, CL-cytc(III) undergoes reversible nitrosylation, whereas between pH 7.9 and 9.5 CL-cytc(III) undergoes irreversible reductive nitrosylation leading to the formation of CL-cytc(II)-NO. Over the whole pH range explored, first-order kinetics of NO binding to CL-cytc(III) (k = 9.3 s(-1) ) indicates that ligand binding is limited by the cleavage of the weak heme-Fe distal bond. Between pH 7.9 and 9.5, nitrosylated CL-cytc(III) converts to the ligand-free ferrous derivative (CL-cytc(II)), this process being pH-dependent (hOH- = 3.0 × 10(3) M(-1) s(-1) ). Then, CL-cytc(II) converts to nitrosylated CL-cytc(II), in the presence of NO excess. The value of the second-order rate constant for CL-cytc(II) nitrosylation is essentially pH-independent, the average value of lon being 1.4 × 10(7) M(-1) s(-1) . These results agree with the view that CL-cytc nitrosylation may play a role in apoptosis regulation.

Keywords: NO binding to the cardiolipin-ferric cytochrome c complex; NO binding to the cardiolipin-ferrous cytochrome c complex; cardiolipin-ferric cytochrome c complex; kinetics.; reductive nitrosylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cardiolipins / metabolism*
  • Cattle
  • Cytochromes c / metabolism*
  • Heme / metabolism
  • Horses
  • Hydrogen-Ion Concentration
  • Iron / metabolism
  • Kinetics
  • Models, Biological
  • Multiprotein Complexes / metabolism*
  • Myocardium / metabolism*
  • Nitric Oxide / metabolism*
  • Oxidation-Reduction

Substances

  • Cardiolipins
  • Multiprotein Complexes
  • Nitric Oxide
  • Heme
  • Cytochromes c
  • Iron