Reactive oxygen species, oxidative stress, and cell death correlate with level of CoQ ₁₀ deficiency

Abstract

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.— Quinzii, C. M., Lopez, L. C., Gilkerson, R. W., Dorado, B., Coku, J., Naini, A. B., Lagier‐Tourenne, C., Schuelke, M., Salviati, L., Carrozzo, R., Santorelli, F., Rahman, S., Tazir, M., Koenig, M., DiMauro, S., Hirano, M. Reactive oxygen species, oxidative stress, and cell death correlate with level of CoQ 10 deficiency. FASEB J. 24, 3733–3743 (2010). www.fasebj.org