title: Reactive oxygen species, oxidative stress, and cell death correlate with level of CoQ10 deficiency.
abstract: Coenzyme Q(10) (CoQ(10)) is essential for electron transport in the mitochondrial respiratory chain and antioxidant defense. The relative importance of respiratory chain defects, ROS production, and apoptosis in the pathogenesis of CoQ(10) deficiency is unknown. We determined previously that severe CoQ(10) deficiency in cultured skin fibroblasts harboring COQ2 and PDSS2 mutations produces divergent alterations of bioenergetics and oxidative stress. Here, to better understand the pathogenesis of CoQ(10) deficiency, we have characterized the effects of varying severities of CoQ(10) deficiency on ROS production and mitochondrial bioenergetics in cells harboring genetic defects of CoQ(10) biosynthesis. Levels of CoQ(10) seem to correlate with ROS production; 10-15% and >60% residual CoQ(10) are not associated with significant ROS production, whereas 30-50% residual CoQ(10) is accompanied by increased ROS production and cell death. Our results confirm that varying degrees of CoQ(10) deficiency cause variable defects of ATP synthesis and oxidative stress. These findings may lead to more rational therapeutic strategies for CoQ(10) deficiency.
authors.affiliation: Department of Neurology, Columbia University Medical Center, 630 W. 168th St., P&S 4-423, New York, NY 10032, USA.
authors.forename: Catarina M
authors.initials: CM
authors.lastname: Quinzii
authors.forename: Luis C
authors.initials: LC
authors.lastname: López
authors.forename: Robert W
authors.initials: RW
authors.lastname: Gilkerson
authors.forename: Beatriz
authors.initials: B
authors.lastname: Dorado
authors.forename: Jorida
authors.initials: J
authors.lastname: Coku
authors.forename: Ali B
authors.initials: AB
authors.lastname: Naini
authors.forename: Clotilde
authors.initials: C
authors.lastname: Lagier-Tourenne
authors.forename: Markus
authors.initials: M
authors.lastname: Schuelke
authors.forename: Leonardo
authors.initials: L
authors.lastname: Salviati
authors.forename: Rosalba
authors.initials: R
authors.lastname: Carrozzo
authors.forename: Filippo
authors.initials: F
authors.lastname: Santorelli
authors.forename: Shamima
authors.initials: S
authors.lastname: Rahman
authors.forename: Meriem
authors.initials: M
authors.lastname: Tazir
authors.forename: Michel
authors.initials: M
authors.lastname: Koenig
authors.forename: Salvatore
authors.initials: S
authors.lastname: DiMauro
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
mesh_terms: D016923:Cell Death; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000378:metabolism; D004734:Energy Metabolism; D006801:Humans; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000172:deficiency
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D014451:Ubiquinone; C024989:coenzyme Q10