title: Lack of β, β-carotene-9', 10'-oxygenase 2 leads to hepatic mitochondrial dysfunction and cellular oxidative stress in mice.
abstract: β,β-Carotene-9',10'-dioxygenase 2 (BCO2) is a carotenoid cleavage enzyme localized to the inner mitochondrial membrane in mammals. This study was aimed to assess the impact of genetic ablation of BCO2 on hepatic oxidative stress through mitochondrial function in mice.
  
  
  
  Liver samples from 6-wk-old male BCO2-/-knockout (KO) and isogenic wild-type (WT) mice were subjected to proteomics and functional activity assays. Compared to the WT, KO mice consumed more food (by 18%) yet displayed significantly lower body weight (by 12%). Mitochondrial proteomic results demonstrated that loss of BCO2 was associated with quantitative changes of the mitochondrial proteome mainly shown by suppressed expression of enzymes and/or proteins involved in fatty acid β-oxidation, the tricarboxylic acid cycle, and the electron transport chain. The mitochondrial basal respiratory rate, proton leak, and electron transport chain complex II capacity were significantly elevated in the livers of KO compared to WT mice. Moreover, elevated reactive oxygen species and increased mitochondrial protein carbonylation were also demonstrated in liver of KO mice.
  
  
  
  Loss of BCO2 induces mitochondrial hyperactivation, mitochondrial stress, and changes of the mitochondrial proteome, leading to mitochondrial energy insufficiency. BCO2 appears to be critical for proper hepatic mitochondrial function.
authors.affiliation: Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, OK, USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Hartson
authors.affiliation: Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA.
authors.forename: Mary Abby
authors.initials: MA
authors.lastname: Davis
authors.affiliation: Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: He
authors.affiliation: Graduate School, University of Missouri-Kansas City, Kansas City, MO, USA.
authors.forename: Denis M
authors.initials: DM
authors.lastname: Medeiros
authors.affiliation: Department of Food, Nutrition, Dietetics, and Health, Kansas State University, Manhattan, KS, USA.
authors.forename: Weiqun
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Clarke
authors.affiliation: Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA.
authors.forename: Edralin A
authors.initials: EA
authors.lastname: Lucas
authors.affiliation: Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA.
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Smith
authors.affiliation: Department of Pharmacology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Johannes
authors.initials: J
authors.lastname: von Lintig
authors.affiliation: Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA.
authors.forename: Dingbo
authors.initials: D
authors.lastname: Lin
mesh_terms: D000818:Animals; D049308:Dioxygenases / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008930:Mitochondria, Liver / Q000235:genetics / Q000473:pathology*; D018384:Oxidative Stress; D050050:Protein Carbonylation; D020543:Proteome / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D020543:Proteome; D017382:Reactive Oxygen Species; D049308:Dioxygenases; C481678:Bco2 protein, mouse
keywords: Liver; Mitochondrial dysfunction; Mitochondrial proteome; Oxidative stress; β, β-Carotene-9′, 10′-oxygenase 2 (BCO2)