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

Citations Over TimeTop 10% of 2007 papers

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.

Related Papers

• → Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors(2005)1,232 cited
• → Role of reactive oxygen species and cardiolipin in the release of cytochrome c from mitochondria(2003)382 cited
• → Cardiolipin oxidation sets cytochrome c free(2005)146 cited
• → The cardiolipin-binding domain of Bid affects mitochondrial respiration and enhances cytochrome c release(2004)55 cited
• → Plant peroxidases. Their primary, secondary and tertiary structures, and relation to cytochrome c peroxidase(1985)169 cited