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lüll Cytochrome c/cardiolipin relations in mitochondria: a kiss of death Kagan VE; Bayir HA; Belikova NA; Kapralov O; Tyurina YY; Tyurin VA; Jiang J; Stoyanovsky DA; Wipf P; Kochanek PM; Greenberger JS; Pitt B; Shvedova AA; Borisenko GFree Radic Biol Med 2009[Jun]; 46 (11): 1439-53Recently, phospholipid peroxidation products gained a reputation as key regulatory molecules and participants in oxidative signaling pathways. During apoptosis, a mitochondria-specific phospholipid, cardiolipin (CL), interacts with cytochrome c (cyt c) to form a peroxidase complex that catalyzes CL oxidation; this process plays a pivotal role in the mitochondrial stage of the execution of the cell death program. This review is focused on redox mechanisms and essential structural features of cyt c's conversion into a CL-specific peroxidase that represent an interesting and maybe still unique example of a functionally significant ligand change in hemoproteins. Furthermore, specific characteristics of CL in mitochondria--its asymmetric transmembrane distribution and mechanisms of collapse, the regulation of its synthesis, remodeling, and fatty acid composition--are given significant consideration. Finally, new concepts in drug discovery based on the design of mitochondria-targeted inhibitors of cyt c/CL peroxidase and CL peroxidation with antiapoptotic effects are presented.|Animals[MESH]|Apoptosis[MESH]|Cardiolipins/*physiology[MESH]|Cytochromes c/*physiology[MESH]|Humans[MESH]|Lipid Peroxidation/physiology[MESH]|Mitochondria/*physiology[MESH]|Oxidative Stress[MESH]|Protein Binding[MESH]|Signal Transduction[MESH] |