title: Probing a complex of cytochrome c and cardiolipin by magnetic circular dichroism spectroscopy: implications for the initial events in apoptosis.
abstract: Oxidation of cardiolipin (CL) by its complex with cytochrome c (cyt c) plays a crucial role in triggering apoptosis. Through a combination of magnetic circular dichroism spectroscopy and potentiometric titrations, we show that both the ferric and ferrous forms of the heme group of a CL:cyt c complex exist as multiple conformers at a physiologically relevant pH of 7.4. For the ferric state, these conformers are His/Lys- and His/OH(-)-ligated. The ferrous state is predominantly high-spin and, most likely, His/-. Interconversion of the ferric and ferrous conformers is described by a single midpoint potential of -80 ± 9 mV vs SHE. These results suggest that CL oxidation in mitochondria could occur by the reaction of molecular oxygen with the ferrous CL:cyt c complex in addition to the well-described reaction of peroxides with the ferric form.
authors.affiliation: Centre for Molecular and Structural Biochemistry, School of Chemistry and School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, Norfolk NR4 7TJ, UK.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Bradley
authors.forename: Gary
authors.initials: G
authors.lastname: Silkstone
authors.forename: Michael T
authors.initials: MT
authors.lastname: Wilson
authors.forename: Myles R
authors.initials: MR
authors.lastname: Cheesman
authors.forename: Julea N
authors.initials: JN
authors.lastname: Butt
mesh_terms: D000818:Animals; D017209:Apoptosis; D002308:Cardiolipins / Q000737:chemistry / Q000378:metabolism*; D002942:Circular Dichroism; D045304:Cytochromes c / Q000737:chemistry / Q000378:metabolism*; D006418:Heme / Q000737:chemistry / Q000378:metabolism; D006736:Horses; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011199:Potentiometry; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D002308:Cardiolipins; D006418:Heme; D045304:Cytochromes c