A new ubiquinone metabolite and its activity at the mitochondrial bc1 complex.

Ubichromanol, a reductive cyclization product of ubiquinone, acts as radical scavenging antioxidant and is similarly effective as alpha-tocopherol. However, nothing is known so far on the two-electron oxidation product of this antioxidant and its bioactivity. This study demonstrates that ubichromanol yields a ubiquinone-like compound with a hydroxyl-substituted side chain (UQOH) on oxidation. HPLC/MS and HPLC/ECD measurements revealed its natural presence in bovine liver mitochondria. The bioactivity of this formerly unknown compound as substrate for mitochondrial complex III was tested by measurements of the quinol:cytochrome c oxidoreductase activity in bovine submitochondrial particles and isolated mitochondrial bc1 complex. Consistently in both model systems, reduced UQOH exhibited substrate efficiencies below that of native ubiquinone but a significantly higher efficiency than alpha-tocopheryl quinone. Model calculations revealed that on binding of reduced UQOH to the bc1 complex the polar hydroxyl group was located close to hydrophobic amino acid residues. This fact could in part explain the lower efficiency of reduced UQOH in comparison to ubiquinone as a substrate for the mitochondrial bc1 complex. Therefore, the hydroxylation of the aliphatic or isoprenoid side chains of bioquinones, which is typical for quinoid oxidation products of chromanols, such as alpha-tocopherol and ubichromanol, disturbs substrate binding at the mitochondrial electron-transfer complexes, which usually interact with ubiquinone.