the consequence of severe CoQ10 deficiency on bioenergetics, oxidative stress, and antioxidant defenses in cultured skin fibroblasts harboring COQ2 mutations is examined. COQ2 mutant fibroblasts have 30% CoQ10 with partial defect in ATP synthesis, as well as significantly increased reactive oxygen species production and oxidation of lipids and proteins
cell viability in skin fibroblasts with CoQ10 deficiency due to different molecular defects including mutations in COQ2. Treatment of multiple cell lines with increasing dosages of 4-nitrobenzoate, which inhibits 4-hydroxybenzoate:polyprenyltransferase, leads to dose-dependent decreases of CoQ in mammalian cells without directly inducing oxidative stress or mitochondrial respiration impairment. Fibroblasts from a patient with a homozygous COQ2 mutation require uridine to maintain cell growth and proposed that deficiency of CoQ10 impaired pyrimidine biosynthesis due to dependence of dihydro-orotate dehydrogenase on ubiquinol. Oxidative stress plays an important role in the demise of COQ2 mutant fibroblasts by activating cell-death related pathways, which are averted by antioxidant supplementation
CoQ10 deficiency caused by mutation S109N in para-hydroxybenzoate-polyprenyl transferase, COQ2, leads to early myoclonic epilepsy, hypertrophic cardiomyopathy and subsequently a nephrotic syndrome, phenotype and clinical features, detailed overview
enzyme mutations cause reduced CoQ10 levels, renal dysfunction associated with mitochondriopathies, and/or an epileptic phenotype, overview. The prevalence of renal symptoms in COQ2 defects may be related to differential expression of proteins involved in ubiquinone metabolism
the enzyme is involved in menaquinone biosynthesis. Blocking ubiquinone synthesis pathway by site-directed mutagenesis of the active site of UbiA in Elizabethkingia meningoseptica is a promising strategy to increase menaquinone K production in Elizabethkingia meningoseptica