Mitochondrial permeability transition induced by reactive oxygen species is independent of cholesterol-regulated membrane fluidity.
Cholesterol enrichment of rat liver mitochondria (CHM) impairs atractyloside-induced mitochondrial permeability transition (MPT) due to decreased membrane fluidity. In this study we addressed the effect of cholesterol enrichment on MPT induced by reactive oxygen species (ROS). Superoxide anion generated by xanthine plus xanthine oxidase triggered mitochondrial swelling and cytochrome c release in CHM, which was prevented by butylated hydroxytoluene, an anti-voltage-dependent anion channel antibody, or cyclosporin A. Furthermore, hydrogen peroxide generated by the combination of ganglioside GD3 and mitochondrial GSH depletion elicited mitochondrial swelling and release of cytochrome c, Smac/Diablo and apoptosis-inducing factor in control mitochondria and CHM. Thus, ROS induce MPT and apoptosome activation regardless of decreased mitochondrial membrane dynamics due to cholesterol enrichment.
Institut de Malalties Digestives, Hospital Clínic y Provincial, Instituto Investigaciones Biomédicas August Pi Suñer, C/Villarroel 170, 08036 Barcelona, Spain.
Anna
A
Colell
Carmen
C
García-Ruiz
Montserrat
M
Mari
José C
JC
Fernández-Checa
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051033:Apoptosis Inducing Factor; D001278:Atractyloside / Q000494:pharmacology; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D045304:Cytochromes c / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005420:Flavoproteins / Q000187:drug effects / Q000378:metabolism; D005732:Gangliosides / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000633:toxicity; D008560:Membrane Fluidity; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism*; D016877:Oxidants / Q000633:toxicity; D010539:Permeability; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
C494831:Aifm1 protein, rat; D000975:Antioxidants; D051033:Apoptosis Inducing Factor; D004791:Enzyme Inhibitors; D005420:Flavoproteins; D005732:Gangliosides; D008565:Membrane Proteins; D016877:Oxidants; D017382:Reactive Oxygen Species; D001278:Atractyloside; D002084:Butylated Hydroxytoluene; C026226:ganglioside, GD3; D016572:Cyclosporine; D045304:Cytochromes c; D002784:Cholesterol; D006861:Hydrogen Peroxide