title: Cytochrome c/cardiolipin relations in mitochondria: a kiss of death.
abstract: Recently, 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.
authors.affiliation: Center for Free Radical and Antioxidant Health, Pittsburgh, PA 15219, USA. kagan@pitt.edu
authors.forename: Valerian E
authors.initials: VE
authors.lastname: Kagan
authors.forename: Hülya A
authors.initials: HA
authors.lastname: Bayir
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Belikova
authors.forename: Olexandr
authors.initials: O
authors.lastname: Kapralov
authors.forename: Yulia Y
authors.initials: YY
authors.lastname: Tyurina
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Tyurin
authors.forename: Jianfei
authors.initials: J
authors.lastname: Jiang
authors.forename: Detcho A
authors.initials: DA
authors.lastname: Stoyanovsky
authors.forename: Peter
authors.initials: P
authors.lastname: Wipf
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
authors.forename: Joel S
authors.initials: JS
authors.lastname: Greenberger
authors.forename: Bruce
authors.initials: B
authors.lastname: Pitt
authors.forename: Anna A
authors.initials: AA
authors.lastname: Shvedova
authors.forename: Grigory
authors.initials: G
authors.lastname: Borisenko
mesh_terms: D000818:Animals; D017209:Apoptosis; D002308:Cardiolipins / Q000502:physiology*; D045304:Cytochromes c / Q000502:physiology*; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology; D008928:Mitochondria / Q000502:physiology*; D018384:Oxidative Stress; D011485:Protein Binding; D015398:Signal Transduction
chemical_list: D002308:Cardiolipins; D045304:Cytochromes c