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

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• 作者：Liana V. Basova ; Igor V. Kurnikov ; Lei Wang ; Vladimir B. Ritov ; Natalia A. Belikova ; Irina I. Vlasova ; Andy A. Pacheco ; Daniel E. Winnica ; Jim Peterson ; Hü ; lya Bayir ; David H. Waldeck ; and ; Valerian
• 刊名：Biochemistry
• 出版年：2007
• 出版时间：March 20, 2007
• 年：2007
• 卷：46
• 期：11
• 页码：3423 - 3434
• 全文大小：222K
• 年卷期：v.46,no.11(March 20, 2007)
• ISSN：1520-4995

文摘

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 incells 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 mitochondrialfunctions. Using cyclic voltammetry and equilibrium redox titrations, we show that the redox potential ofcyt c shifts negatively by 350-400 mV upon binding to CL-containing membranes. Consequently, functionsof 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 byascorbate. Thus, both redox properties and functions of cyt c change upon interaction with CL in themitochondrial membrane, diminishing cyt c's electron donor/acceptor role and stimulating its peroxidaseactivity.