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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
07:42

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c

Published on: June 29, 2011

Cardiolipin drives cytochrome c proapoptotic and antiapoptotic actions

Paolo Ascenzi1, Fabio Polticelli, Maria Marino

  • 1Interdepartmental Laboratory for Electron Microscopy, Via della Vasca Navale 79, Roma, Italy. ascenzi@uniroma3.it

IUBMB Life
|March 30, 2011
PubMed

Insights

Cardiolipin (CL) binding to cytochrome c (cytc) alters its structure and function. This CL-cytc complex exhibits dual roles, potentially promoting or inhibiting apoptosis through various mechanisms.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cellular Biology

Background:

  • Cytochrome c (cytc) is essential for mitochondrial respiration and apoptosis.
  • Native horse heart cytc (hhcytc) has low ligand reactivity and no catalytic activity due to its hexacoordinated heme-Fe-atom.
  • The interaction of hhcytc with cardiolipin (CL) is crucial for modulating its function.

Purpose of the Study:

  • To review the allosteric modulation of hhcytc properties driven by cardiolipin (CL).
  • To highlight the dual proapoptotic and antiapoptotic actions of the CL-hhcytc complex.

Main Methods:

  • Structural analysis of hhcytc upon interaction with CL.
  • Assessment of the CL-hhcytc complex's midpoint potential.
  • Evaluation of ligand binding affinities (CO, NO) and peroxidase activity.

Main Results:

  • CL binding induces tertiary structural changes in hhcytc, disrupting the heme-Fe-Met80 bond.
  • The CL-hhcytc complex exhibits altered midpoint potential, high affinity for CO and NO, and peroxidase activity.
  • The complex facilitates peroxynitrite isomerization to nitrate.

Conclusions:

  • The CL-hhcytc complex displays context-dependent proapoptotic effects (lipid peroxidation, cytc release) and antiapoptotic actions (peroxynitrite scavenging, CO/NO binding).
  • CL-driven allosteric modulation of hhcytc results in significant functional diversification.
  • Understanding these dual roles is critical for cellular regulation and disease pathology.

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