title: Cardiolipin-cytochrome c complex: Switching cytochrome c from an electron-transfer shuttle to a myoglobin- and a peroxidase-like heme-protein.
abstract: Cytochrome c (cytc) is a small heme-protein located in the space between the inner and the outer membrane of the mitochondrion that transfers electrons from cytc-reductase to cytc-oxidase. The hexa-coordinated heme-Fe atom of cytc displays a very low reactivity toward ligands and does not exhibit significant catalytic properties. However, upon cardiolipin (CL) binding, cytc achieves ligand binding and catalytic properties reminiscent of those of myoglobin and peroxidase. In particular, the peroxidase activity of the cardiolipin-cytochrome c complex (CL-cytc) is critical for the redistribution of CL from the inner to the outer mitochondrial membranes and is essential for the execution and completion of the apoptotic program. On the other hand, the capability of CL-cytc to bind NO and CO and the heme-Fe-based scavenging of reactive nitrogen and oxygen species may affect apoptosis. Here, the ligand binding and catalytic properties of CL-cytc are analyzed in parallel with those of CL-free cytc, myoglobin, and peroxidase to dissect the potential mechanisms of CL in modulating the pro- and anti-apoptotic actions of cytc.
authors: Interdepartmental Laboratory for Electron Microscopy, Roma Tre University, Roma, Italy.
authors: Paolo
authors: P
authors: Ascenzi
authors: Massimo
authors: M
authors: Coletta
authors: Michael T
authors: MT
authors: Wilson
authors: Laura
authors: L
authors: Fiorucci
authors: Maria
authors: M
authors: Marino
authors: Fabio
authors: F
authors: Polticelli
authors: Federica
authors: F
authors: Sinibaldi
authors: Roberto
authors: R
authors: Santucci
mesh_terms: D000818:Animals; D017209:Apoptosis; D002308:Cardiolipins / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism*; D004579:Electron Transport; D006418:Heme / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D046912:Multiprotein Complexes / Q000378:metabolism; D009211:Myoglobin / Q000378:metabolism; D009572:Nitrite Reductases / Q000378:metabolism; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000378:metabolism / Q000493:pharmacokinetics; D050050:Protein Carbonylation
chemical_list: D002308:Cardiolipins; D046912:Multiprotein Complexes; D009211:Myoglobin; D030421:Peroxynitrous Acid; D006418:Heme; D045304:Cytochromes c; D009572:Nitrite Reductases
keywords: apoptosis; cardiolipin-cytochrome c complex; nitrite reductase activity; peroxidase activity; peroxynitrite detoxification; redox properties