title: Cardiolipin switch in mitochondria: shutting off the reduction of cytochrome c and turning on the peroxidase activity.
abstract: 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.
authors.affiliation: Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Liana V
authors.initials: LV
authors.lastname: Basova
authors.forename: Igor V
authors.initials: IV
authors.lastname: Kurnikov
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Ritov
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Belikova
authors.forename: Irina I
authors.initials: II
authors.lastname: Vlasova
authors.forename: Andy A
authors.initials: AA
authors.lastname: Pacheco
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Winnica
authors.forename: Jim
authors.initials: J
authors.lastname: Peterson
authors.forename: Hülya
authors.initials: H
authors.lastname: Bayir
authors.forename: David H
authors.initials: DH
authors.lastname: Waldeck
authors.forename: Valerian E
authors.initials: VE
authors.lastname: Kagan
mesh_terms: 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
chemical_list: C519576:1,1',2,2'-tetraoleoylcardiolipin; D002308:Cardiolipins; D008081:Liposomes; D045304:Cytochromes c; D010544:Peroxidases; D003576:Electron Transport Complex IV; D001205:Ascorbic Acid