Cardiolipin switch in mitochondria: shutting off the reduction of cytochrome c and turning on the peroxidase activity.
Upon interaction with anionic phospholipids, particularly mitochondria-specific cardiolipin (CL), cytochrome c (cyt c) loses its tertiary structure and its peroxidase activity dramatically increases. CL-induced peroxidase activity of cyt c has been found to be important for selective CL oxidation in cells undergoing programmed death. During apoptosis, the peroxidase activity and the fraction of CL-bound cyt c markedly increase, suggesting that CL may act as a switch to regulate cyt c's mitochondrial functions. Using cyclic voltammetry and equilibrium redox titrations, we show that the redox potential of cyt c shifts negatively by 350-400 mV upon binding to CL-containing membranes. Consequently, functions of cyt c as an electron transporter and cyt c reduction by Complex III are strongly inhibited. Further, CL/cyt c complexes are not effective in scavenging superoxide anions and are not effectively reduced by ascorbate. Thus, both redox properties and functions of cyt c change upon interaction with CL in the mitochondrial membrane, diminishing cyt c's electron donor/acceptor role and stimulating its peroxidase activity.
Basova
Liana V
LV
Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Kurnikov
Igor V
IV
Wang
Lei
L
Ritov
Vladimir B
VB
Belikova
Natalia A
NA
Vlasova
Irina I
II
Pacheco
Andy A
AA
Winnica
Daniel E
DE
Peterson
Jim
J
Bayir
Hülya
H
Waldeck
David H
DH
Kagan
Valerian E
VE
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D002308:Cardiolipins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D045304:Cytochromes c / Q000378:metabolism*; D004563:Electrochemistry; D004578:Electron Spin Resonance Spectroscopy; D003576:Electron Transport Complex IV / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
C519576:1,1',2,2'-tetraoleoylcardiolipin; D002308:Cardiolipins; D008081:Liposomes; D045304:Cytochromes c; D010544:Peroxidases; D003576:Electron Transport Complex IV; D001205:Ascorbic Acid