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Cardiolipin and Its Redox Interactions With Cytochrome c In Apoptosis
Author(s) -
Kagan Valerian E.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.80.3
Subject(s) - cardiolipin , cytochrome c , chemistry , phosphatidylserine , mitochondrion , peroxidase , cytosol , biochemistry , redox , cytochrome , phospholipid hydroperoxide glutathione peroxidase , apoptosis , lipid peroxidation , apoptosome , phospholipid , voltage dependent anion channel , microbiology and biotechnology , membrane , biology , enzyme , catalase , caspase , programmed cell death , bacterial outer membrane , glutathione peroxidase , organic chemistry , escherichia coli , gene
During apoptosis cytochrome c (cyt c) interacts with cardiolipin (CL) and obtains a new catalytic function as a CL‐specific peroxidase that causes oxidation of CL in mitochondria. Fatty acid hydroperoxides are ~1,000 times more effective as sources of oxidizing equivalents for the peroxidase function of cyt c/CL than H2O2. Migration of CL from the inner to the outer mitochondrial membrane is a pre‐requisite for its interaction with cyt c. Thus, CL acts as a redox switch that turns off the electron transporting function of cyt c and turns on its peroxidase activity. Mitochondria‐targeted inhibitors of CL peroxidation act as potent anti‐apoptotic agents thus offering new opportunities for drug discovery. In the cytosol, released cyt c interacts with another anionic phospholipid, phosphatidylserine (PS), and catalyzes its oxidation. Peroxidation facilitates PS externalization ‐ essential for the recognition and clearance of apoptotic cells by macrophages.