Ubichromanol: A prodrug to support mitochondrial ubiquinone functions?

Ubichromanol‐9 (UCa 9 , 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 10 OH), 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 bc 1 complex) was slightly below that of native ubiquinol, but significantly higher than that of reduced α‐tocopheryl quinone. Since ubiquinone‐like molecules (UQ 10 OH, UQ 10 ) were identified as oxidation products of UCa 9 during lipid peroxidation, this ubiquinone derivative could provide a possibility to combine antioxidant properties of chromanols and bioenergetic benefits of UQ 10 .