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

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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.

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Abbreviations

CL:

Cardiolipin

CL-cytc :

Cardiolipin-bound cytc

CL-cytc-Fe(II):

Cardiolipin-bound cytc-Fe(II)

CL-cytc-Fe(II)-NO:

Cardiolipin-bound cytc-Fe(II)-NO

CL-cytc-Fe(III):

Cardiolipin-bound cytc-Fe(III)

cytc :

Cytochrome c

cytc-Fe(III):

Ferric cytochrome c

cytc-Fe(II):

Ferrous cytochrome c

cytc-Fe(II)-NO:

Nitrosylated cytc-Fe(II)

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Acknowledgments

This work was supported by grants from the Ministero dell’Istruzione, dell’Università e della Ricerca of Italy (PRIN 2010–2011 grant no. 20109MXHMR_001, and University Roma Tre, CLA 2013, to P.A.).

Author information

Authors and Affiliations

  1. Interdepartmental Laboratory for Electron Microscopy, University Roma Tre, Via della Vasca Navale 79, 00146, Rome, Italy

    Paolo Ascenzi

  2. Department of Sciences, University Roma Tre, Viale Marconi 446, 00146, Rome, Italy

    Maria Marino & Fabio Polticelli

  3. National Institute of Nuclear Physics, University Roma Tre Section, Via della Vasca Navale 84, 00146, Rome, Italy

    Fabio Polticelli

  4. Department of Clinical Sciences and Translational Medicine, University of Roma “Tor Vergata”, Via Montpellier 1, 00133, Rome, Italy

    Roberto Santucci & Massimo Coletta

  5. Interuniversity Consortium for the Research on the Chemistry of Metals in Biological Systems, Via Celso Ulpiani 27, 70126, Bari, Italy

    Roberto Santucci & Massimo Coletta

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  1. Paolo Ascenzi
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  2. Maria Marino
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  3. Fabio Polticelli
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  4. Roberto Santucci
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  5. Massimo Coletta
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Correspondence to Paolo Ascenzi.

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Ascenzi, P., Marino, M., Polticelli, F. et al. Cardiolipin modulates allosterically the nitrite reductase activity of horse heart cytochrome c . J Biol Inorg Chem 19, 1195–1201 (2014). https://doi.org/10.1007/s00775-014-1175-9

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  • DOI: https://doi.org/10.1007/s00775-014-1175-9

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