Cardiolipin drives cytochrome c proapoptotic and antiapoptotic actions

Abstract

SummaryCytochrome 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 CLhhcytc 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 NO 3 2 , 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, or antiapoptotic 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.

Subtle Change in the Charge Distribution of Surface Residues May Affect the Secondary Functions of Cytochrome c

“…The interaction between cyt c and CDL has been studied and reviewed extensively in the (5,30,38,60,61). The data presented here are described schematically in Fig.…”

NO2−-mediated nitrosylation of ferrous microperoxidase-11

“…CL-cyt c could exert a pro-apoptotic effect catalyzing the CL peroxidation, which has been proposed to favor the cyt c mobilization to cytosol where it triggers apoptosis, engaging the apoptotic protease-activating factor-1, and forming the apoptosome. However, CL-cyt c can play an anti-apoptotic role by binding CO and NO that could inhibit the peroxidase activity and the translocation of cyt c in the cytosol, and by scavenging reactive nitrogen and oxygen species (e.g., peroxynitrite) [2,7,61,62].…”

Effects of silk sericin on the proliferation and apoptosis of colon cancer cells

“…Late apoptosis involves fragmentation of nuclear chromatin. The stages of apoptosis depend on differential apoptotic stimuli, as well as functions of anti-apoptotic and pro-apoptotic proteins (Indran et al, 2011;Kelly et al, 2011;Ascenzi et al, 2011). Malignant transformation of epithelial cells, including those of the colon, also involves various proteins that promote or inhibit apoptosis at different stages (Royer and Lu, 2011).…”