Cardiolipin Switch in Mitochondria:  Shutting off the Reduction of Cytochrome c and Turning on the Peroxidase Activity

LV Basova, IV Kurnikov, L Wang, VB Ritov… - Biochemistry, 2007 - ACS Publications
LV Basova, IV Kurnikov, L Wang, VB Ritov, NA Belikova, II Vlasova, AA Pacheco…
Biochemistry, 2007ACS Publications
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 …
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.
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