Ubichromanol: A prodrug to support mitochondrial ubiquinone functions?

Ubichromanol-9 (UCa₉, with a side chain consisting of nine isoprene units) is a reductive cyclization product of ubiquinone-10 (UQ ₁₀). It acts as a radical scavenging antioxidant and is about half as effective as α-tocopherol. Already decades ago its one-electron oxidation product, the ubichromanoxyl radical had been identified. However, nothing was known so far about the two-electron oxidation product of this antioxidant and its bioactivity. This study proves that ubichromanol can be oxidized to a ubiquinone-like compound with a hydroxyl-substituted side chain (UQ ₁₀OH), a metabolite that is naturally present in bovine liver mitochondria. The bioactivity of this ubiquinone derivative in its reduced form as substrate for mitochondrial complex III (cytochrome bc₁ complex) was slightly below that of native ubiquinol, but significantly higher than that of reduced α-tocopheryl quinone. Since ubiquinone-like molecules (UQ ₁₀OH, UQ₁₀) were identified as oxidation products of UCa₉ during lipid peroxidation, this ubiquinone derivative could provide a possibility to combine antioxidant properties of chromanols and bioenergetic benefits of UQ₁₀.