A role of flavonoids in cytochrome c-cardiolipin interactions. (1st March 2021)

• Record Type: Journal Article
• Authors: Rice, Malaysha; Wong, Bokey; Oja, Mare; Samuels, Kelley; Williams, Alicia K.; Fong, Jenny; Sapse, Anne-Marie; Maran, Uko; Korobkova, Ekaterina A.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 33(2021)
• Publication Date: 2021-03-01
• Subjects: Cardiolipin -- Flavonoid -- Cytochrome c -- Liposome -- Mitochondrial apoptosis -- Membrane permeability; Cyt c cytochrome c -- CL cardiolipin -- PC phosphocholine -- AR Amplex Red -- ROS reactive oxygen species -- DMSO dimethyl sulfoxide -- HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid -- SDS sodium dodecyle sulfate -- MPT mitochondrial permeability transition -- EGCG epigallocatechin gallate -- MLV multilamellar vesicle -- SUV small unilamellar vesicle -- GuHCl guanidinium chloride -- DPPH 2, 2-diphenyl-1-picrylhydrazyl -- PAMPA parallel artificial membrane permeability assay -- PSA polar surface area -- DFT Density Functional Theory; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2021.116043
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: The processes preceding the detachment of cytochrome c (cyt c) from the inner mitochondrial membrane in intrinsic apoptosis involve peroxidation of cardiolipin (CL) catalyzed by cyt c-CL complex. In the present work, we studied the effect of 17 dietary flavonoids on the peroxidase activity of cyt c bound to liposomes. Specifically, we explored the relationship between peroxidase activity and flavonoids' (1) potential to modulate cyt c unfolding, (2) effect on the oxidation state of heme iron, (3) membrane permeability, (4) membrane binding energy, and (5) structure. The measurements revealed that flavones, flavonols, and flavanols were the strongest, while isoflavones were the weakest inhibitors of the oxidation. Flavonoids' peroxidase inhibition activity correlated positively with their potential to suppress Trp-59 fluorescence in cyt c as well as the number of OH groups. Hydrophilic flavonoids, such as catechin, having the lowest membrane permeability and the strongest binding with phosphocholine (PC) based on the quantum chemical calculations exhibited the strongest inhibition of Amplex Red (AR) peroxidation, suggesting a membrane-protective function of flavonoids at the surface. The results of the present research specify basic principles for the design of molecules that will control the catalytic oxidation of lipids in mitochondrial membranes. These principles take into account the number of hydroxyl groups and hydrophilicity of flavonoids.