title: The interaction of antioxidants and structurally related compounds with mitochondrial oxidative phosphorylation.
abstract: The antioxidants, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), interact with mitochondrial oxidative phosphorylation in two ways. They uncouple phosphorylation from oxidation by making the mitochondrial inner membrane more permeable to protons. They also inhibit respiration by a direct interaction with the electron transport chain. Here we separated out these two properties of BHA and BHT by determining their effects on respiration in coupled and uncoupled mitochondria. Similar experiments were carried out with compounds structurally related to BHA and BHT. Most of these compounds had uncoupling and inhibitory properties essentially similar to BHA and BHT. In contrast, the dimer of BHA had no inhibitory effects on uncoupled respiration and little uncoupling activity. The implications of these results for the interactions of BHA and BHT with mitochondrial oxidative phosphorylation and the design of antioxidants are discussed.
authors.affiliation: Department of Biochemistry, Trinity College, Dublin, Ireland.
authors.forename: F
authors.initials: F
authors.lastname: Fusi
authors.forename: M
authors.initials: M
authors.lastname: Valoti
authors.forename: G
authors.initials: G
authors.lastname: Sgaragli
authors.forename: M P
authors.initials: MP
authors.lastname: Murphy
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002083:Butylated Hydroxyanisole / Q000494:pharmacology*; D002084:Butylated Hydroxytoluene / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004579:Electron Transport / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000975:Antioxidants; D002084:Butylated Hydroxytoluene; D002083:Butylated Hydroxyanisole