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Cardiolipin switch in mitochondria: shutting off the reduction of cytochrome C and turning on the peroxidase activity.
Basova LV; Kurnikov IV; Wang L; Ritov VB; Belikova NA; Vlasova II; Pacheco AA; Winnica DE; Peterson J; Bayir H; Waldeck DH; Kagan VE
Biochemistry 2007 Mar; 46(11):3423-3434
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.
Metabolism; Pharmacology; Cell-metabolism; Enzymes; Enzyme-activity; Lipids; Lipid-peroxidation; Oxidation-reduction-reactions; Oxidation; Electrophysiology; Cellular-transport-mechanism; Cellular-structures
Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260
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Issue of Publication
University of Pittsburgh at Pittsburgh
Page last reviewed: August 12, 2022
Content source: National Institute for Occupational Safety and Health Education and Information Division