Cardiolipin modulates allosterically the nitrite reductase activity of horse heart cytochrome c

Paolo Ascenzi, Maria Marino, Fabio Polticelli, Roberto Santucci, Massimo Coletta

Research output: Contribution to journalArticlepeer-review

Abstract

Upon cardiolipin (CL) liposomes binding, horse heart cytochrome c (cytc) changes its tertiary structure disrupting the heme-Fe-Met80 distal bond, reduces drastically the midpoint potential, binds CO and NO with high affinity, displays peroxidase activity, and facilitates peroxynitrite isomerization. Here, the effect of CL liposomes on the nitrite reductase activity of ferrous cytc (cytc-Fe(II)) is reported. In the absence of CL liposomes, hexa-coordinated cytc-Fe(II) displays a very low value of the apparent second-order rate constant for the NO2 --mediated conversion of cytc-Fe(II) to cytc-Fe(II)-NO (k on = (7.3 ± 0.7) × 10-2 M-1 s-1; at pH 7.4 and 20.0 °C). However, CL liposomes facilitate the NO2 --mediated nitrosylation of cytc-Fe(II) in a dose-dependent manner inducing the penta-coordination of the heme-Fe(II) atom. The value of k on for the NO2 --mediated conversion of CL-cytc-Fe(II) to CL-cytc-Fe(II)-NO is 2.6 ± 0.3 M-1 s-1 (at pH 7.4 and 20.0°C). Values of the apparent dissociation equilibrium constant for CL liposomes binding to cytc-Fe(II) are (2.2 ± 0.2) × 10-6 M, (1.8 ± 0.2) × 10-6 M, and (1.4 ± 0.2) × 10-6 M at pH 6.5, 7.4, and 8.1, respectively, and 20.0°C. These results suggest that the NO2 --mediated conversion of CL-cytc-Fe(II) to CL-cytc-Fe(II)-NO could play anti-apoptotic effects impairing lipid peroxidation and therefore the initiation of the cell death program by the release of pro-apoptotic factors (including cytc) in the cytoplasm.

Original languageEnglish
Pages (from-to)1195-1201
Number of pages7
JournalJournal of Biological Inorganic Chemistry
Volume19
Issue number7
DOIs
Publication statusPublished - Jun 27 2014

Keywords

  • Allostery
  • Cardiolipin
  • Horse heart cytochrome c
  • Nitrite reductase activity
  • Nitrite-mediated nitrosylation

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry
  • Medicine(all)

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