Cardiolipin drives cytochrome c proapoptotic and antiapoptotic actions

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

Research output: Contribution to journalArticle

Abstract

Cytochrome c (cytc) is pivotal in mitochondrial respiration and apoptosis. The heme-Fe-atom of native hexacoordinated horse heart cytc (hhcytc) displays a very low reactivity toward ligands and does not exhibit catalytic properties. However, on interaction with cardiolipin (CL), hhcytc changes its tertiary structure disrupting the heme-Fe-Met80 distal bond. The CL-hhcytc complex displays a very low midpoint potential, out of the range required for its physiological role, binds CO and NO with high affinity, facilitates peroxynitrite isomerization to NO3 -, and displays peroxidase activity. As a whole, the CL-hhcytc complex could play either proapoptotic effects, catalyzing lipid peroxidation and the subsequent hhcytc release into the cytoplasm, orantiapoptotic actions, such as scavenging peroxynitrite (i.e., protecting the mitochondrion from reactive nitrogen and oxygen species), and binding of CO and NO (i.e., inhibiting lipid peroxidation and hhcytc traslocation). Here, the CL-driven allosteric modulation of hhcytc properties is reviewed, highlighting proapoptotic and antiapoptotic actions.

Original languageEnglish
Pages (from-to)160-165
Number of pages6
JournalIUBMB Life
Volume63
Issue number3
DOIs
Publication statusPublished - Mar 2011

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Keywords

  • allostery
  • apoptosis
  • cardiolipin
  • CO binding
  • cytochrome c
  • lipid peroxidation
  • NO binding
  • peroxynitrite isomerization

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Clinical Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Ascenzi, P., Polticelli, F., Marino, M., Santucci, R., & Coletta, M. (2011). Cardiolipin drives cytochrome c proapoptotic and antiapoptotic actions. IUBMB Life, 63(3), 160-165. https://doi.org/10.1002/iub.440