Reactive oxygen species, oxidative stress, and cell death correlate with level of CoQ10 deficiency.
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.
Quinzii
Catarina M
CM
Department of Neurology, Columbia University Medical Center, 630 W. 168th St., P&S 4-423, New York, NY 10032, USA.
López
Luis C
LC
Gilkerson
Robert W
RW
Dorado
Beatriz
B
Coku
Jorida
J
Naini
Ali B
AB
Lagier-Tourenne
Clotilde
C
Schuelke
Markus
M
Salviati
Leonardo
L
Carrozzo
Rosalba
R
Santorelli
Filippo
F
Rahman
Shamima
S
Tazir
Meriem
M
Koenig
Michel
M
DiMauro
Salvatore
S
Hirano
Michio
M
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
D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D014451:Ubiquinone; C024989:coenzyme Q10