title: Choline and dimethylglycine produce superoxide/hydrogen peroxide from the electron transport chain in liver mitochondria.
abstract: Here, we report that choline and dimethylglycine can stimulate reactive oxygen species (ROS) production in liver mitochondria. Choline stimulated O2˙-/H2O2formation at a concentration of 5 μm. We also observed that Complex II and III inhibitors, atpenin A5 and myxothiazol, collectively induced a 95% decrease in O2˙-/H2O2production indicating both sites serve as the main sources of ROS during choline oxidation. Dimethylglycine, an intermediate of choline oxidation, was a more effective ROS generator. Rates of production were ~ 43% higher than choline-mediated O2˙-/H2O2production. The main site for dimethylglycine-mediated ROS production was via reverse electron transfer to Complex I. Our results demonstrate that metabolism of essential metabolites involved in methionine and folic acid biosynthesis can stimulate mitochondrial ROS production.
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, Canada.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Mailloux
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, Canada.
authors.forename: Adrian
authors.initials: A
authors.lastname: Young
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, Canada.
authors.forename: Julia
authors.initials: J
authors.lastname: Chalker
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, Canada.
authors.forename: Danielle
authors.initials: D
authors.lastname: Gardiner
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, Canada.
authors.forename: Marisa
authors.initials: M
authors.lastname: O'Brien
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, Canada.
authors.forename: Liam
authors.initials: L
authors.lastname: Slade
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, Canada.
authors.forename: John T
authors.initials: JT
authors.lastname: Brosnan
mesh_terms: D000818:Animals; D002794:Choline / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism*; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
chemical_list: D013481:Superoxides; C025138:dimethylglycine; D006861:Hydrogen Peroxide; D002794:Choline; D012521:Sarcosine
keywords: choline; dimethylglycine; mitochondria; one-carbon metabolism; reactive oxygen species