title: Mitochondrial targeting of mouse NQO1 and CYP1B1 proteins.
abstract: Four dioxin-inducible enzymes--NAD(P)H: quinone oxidoreductase-1 (NQO1) and three cytochromes P450 (CYP1A1, CYP1A2 & CYP1B1)--are implicated in both detoxication and metabolic activation of various endobiotics and xenobiotics. NQO1 is generally regarded as a cytosolic enzyme; whereas CYP1 proteins are located primarily in endoplasmic reticulum (ER), CYP1A1 and CYP1A2 proteins are also targeted to mitochondria. This lab has generated Cyp1a1(mc/mc) and Cyp1a1(mtt/mtt) knock-in mouse lines in which CYP1A1 protein is targeted exclusively to ER (microsomes) and mitochondria, respectively. Comparing dioxin-treated Cyp1(+/+) wild-type, Cyp1a1(mc/mc), Cyp1a1(mtt/mtt), and Cyp1a1(-/-), Cyp1b1(-/-) and Nqo1(-/-) knockout mice, in the present study we show that [a] NQO1 protein locates to cytosol, ER and mitochondria, [b] CYP1B1 protein (similar to CYP1A1 and CYP1A2 proteins) traffics to mitochondria as well as ER, and [c] NQO1 and CYP1B1 targeting to mitochondrial or ER membranes is independent of CYP1A1 presence in that membrane.
authors.affiliation: Department of Environmental Health and Center for Environmental Genetics, University Cincinnati Medical Center, Cincinnati, OH 45267-0056, USA.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Dong
authors.forename: Howard G
authors.initials: HG
authors.lastname: Shertzer
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Genter
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
authors.forename: Vasilis
authors.initials: V
authors.lastname: Vasiliou
authors.forename: Colin
authors.initials: C
authors.lastname: Jefcoate
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Nebert
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D002478:Cells, Cultured; D065633:Cytochrome P-450 CYP1B1; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D001189:Aryl Hydrocarbon Hydroxylases; C585498:Cyp1b1 protein, mouse; D065633:Cytochrome P-450 CYP1B1; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse