title: Glutathione metabolism links FOXRED1 to NADH:ubiquinone oxidoreductase (complex I) deficiency: A hypothesis.
abstract: FOXRED1 mutations result in complex I (NADH:ubiquinone oxidoreductase) deficiencies and Leigh syndrome (subacute necrotizing encephalomyelopathy). FOXRED1 is a mitochondrial flavoprotein related to N-methyl amino acid dehydrogenases. How is FOXRED1 required for the biogenesis of complex I? I present a hypothesis that suggests FOXRED1 catalytic activity as a sarcosine oxidase protects the developing fetus from oxidative stress during pregnancy. Loss of FOXRED1, coupled with protein, choline and/or folate-deficient diets results in the depletion of glutathione, the dysregulation of nitric oxide metabolism and the peroxynitrite-mediated inactivation of complex I.
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G2H7, Canada. Electronic address: bernard.lemire@ualberta.ca.
authors.forename: Bernard D
authors.initials: BD
authors.lastname: Lemire
mesh_terms: D042967:Electron Transport Complex I / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007888:Leigh Disease / Q000473:pathology* / Q000503:physiopathology*; D018832:Molecular Chaperones / Q000378:metabolism*; D011247:Pregnancy
chemical_list: C556294:FOXRED1 protein, human; D018832:Molecular Chaperones; D042967:Electron Transport Complex I; D005978:Glutathione
keywords: Glutathione metabolism; Leigh syndrome; NADH:ubiquinone oxidoreductase; Nitric oxide; S nitrosylation; Sarcosine oxidase