title: Cardiolipin drives cytochrome c proapoptotic and antiapoptotic actions.
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
authors: Interdepartmental Laboratory for Electron Microscopy, Via della Vasca Navale 79, Roma, Italy. ascenzi@uniroma3.it
authors: Paolo
authors: P
authors: Ascenzi
authors: Fabio
authors: F
authors: Polticelli
authors: Maria
authors: M
authors: Marino
authors: Roberto
authors: R
authors: Santucci
authors: Massimo
authors: M
authors: Coletta
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D055162:Biocatalysis; D002308:Cardiolipins / Q000502:physiology*; D045304:Cytochromes c / Q000502:physiology*; D006736:Horses; D009206:Myocardium / Q000201:enzymology
chemical_list: D002308:Cardiolipins; D045304:Cytochromes c