title: Elucidating the mechanism of ferrocytochrome c heme disruption by peroxidized cardiolipin.
abstract: The interaction of peroxidized cardiolipin with ferrocytochrome c induces two kinetically and chemically distinct processes. The first is a rapid oxidation of ferrocytochrome c, followed by a slower, irreversible disruption of heme c. The oxidation of ferrocytochrome c by peroxidized cardiolipin is explained by a Fenton-type reaction. Heme scission is a consequence of the radical-mediated reactions initiated by the interaction of ferric heme iron with peroxidized cardiolipin. Simultaneously with the heme c disruption, generation of hydroxyl radical is detected by EPR spectroscopy using the spin trapping technique. The resulting apocytochrome c sediments as a heterogeneous mixture of high aggregates, as judged by sedimentation analysis. Both the oxidative process and the destructive process were suppressed by nonionic detergents and/or high ionic strength. The mechanism for generating radicals and heme rupture is presented.
authors.affiliation: Department of Biochemistry, The University of Texas Health Science Center, San Antonio, TX 78229-3900, USA. musatov@uthscsa.edu
authors.forename: Andrej
authors.initials: A
authors.lastname: Musatov
authors.forename: Marian
authors.initials: M
authors.lastname: Fabian
authors.forename: Rastislav
authors.initials: R
authors.lastname: Varhač
mesh_terms: D000818:Animals; D001059:Apoproteins / Q000737:chemistry / Q000378:metabolism; D002308:Cardiolipins / Q000378:metabolism*; D002417:Cattle; D045304:Cytochromes c / Q000737:chemistry* / Q000378:metabolism*; D006418:Heme / Q000031:analogs & derivatives* / Q000378:metabolism; D007700:Kinetics; D015227:Lipid Peroxidation; D010084:Oxidation-Reduction; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary
chemical_list: D001059:Apoproteins; D002308:Cardiolipins; C031690:heme C; D006418:Heme; D045304:Cytochromes c