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FASEB J. 2010 Oct;24(10):3733-43. doi: 10.1096/fj.09-152728. Epub 2010 May 21.

Reactive oxygen species, oxidative stress, and cell death correlate with level of CoQ10 deficiency.

Author information

1
Department of Neurology, Columbia University Medical Center, 630 W. 168th St., P&S 4-423, New York, NY 10032, USA.

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.

PMID:
20495179
PMCID:
PMC2996902
DOI:
10.1096/fj.09-152728
[Indexed for MEDLINE]
Free PMC Article

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