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

Coenzyme Q₁₀ (CoQ₁₀) 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 CoQ₁₀ deficiency is unknown. We determined previously that severe CoQ₁₀ 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 CoQ₁₀ deficiency, we have characterized the effects of varying severities of CoQ₁₀ deficiency on ROS production and mitochondrial bioenergetics in cells harboring genetic defects of CoQ₁₀ biosynthesis. Levels of CoQ₁₀ seem to correlate with ROS production; 10-15% and >60% residual CoQ₁₀ are not associated with significant ROS production, whereas 30-50% residual CoQ₁₀ is accompanied by increased ROS production and cell death. Our results confirm that varying degrees of CoQ₁₀ deficiency cause variable defects of ATP synthesis and oxidative stress. These findings may lead to more rational therapeutic strategies for CoQ₁₀ deficiency.