Vitamin K2 cannot substitute Coenzyme Q(10) as electron carrier in the mitochondrial respiratory chain of mammalian cells

Coenzyme Q(10) (CoQ(10)) deficiencies are a group of heterogeneous conditions that respond to ubiquinone administration if treated soon after the onset of symptoms. However, this treatment is only partially effective due to its poor bioavailability. We tested whether vitamin K2, which was reported to act as a mitochondrial electron carrier in D. melanogaster, could mimic ubiquinone function in human CoQ(10) deficient cell lines, and in yeast carrying mutations in genes required for coenzyme Q(6) (CoQ(6)) biosynthesis. We found that vitamin K2, despite entering into mitochondria, restored neither electron flow in the respiratory chain, nor ATP synthesis. Conversely, coenzyme Q(4) (CoQ(4)), an analog of CoQ(10) with a shorter isoprenoid side chain, could efficiently substitute its function. Given its better solubility, CoQ(4) could represent an alternative to CoQ(10) in patients with both primary and secondary CoQ(10) deficiencies.