A New Ubiquinone Metabolite and Its Activity at the Mitochondrial bc₁ Complex

Abstract

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.

Antimalarial activity of new acridinone derivatives

“…Bos taurus heart mitochondria was used to isolate cytochrome bc 1 as a mammalian system, fresh bovine hearts (1.2-1.5 kg) were homogenized followed by stepwise differential centrifugation [23]. The bc 1 complex was prepared following the methodology of Schä gger et al [24] modified as described by Gille et al [25].…”

Tocopheryl quinones and mitochondria

“…The ratios were calculated from the concentrations of the respective compounds and multiplied by 100 to obtain mol%. Subcellular fractions were obtained as described in [98] and analyzed after extraction with organic solvents by HPLC with precolumn reduction and electrochemical detection as described in [109].…”

“…Under these conditions, TQ and Toc compete with native UQ 10 for reductase activity of isolated mitochondrial cyt bc 1 complex. Cyt bc 1 complex was prepared as described in [109]. The inhibition of dUQH 2 :cyt c 31 oxidoreductase activity in isolated cyt bc 1 complex (6 nM) was determined in buffer (pH 7.2, 251C) containing 250 mM sucrose, 50 mM KH 2 PO 4 , 0.2 mM EDTA, 2.5 mM KCN, 2 mM NaN 3 and 100 mM cyt c…”

“…In this context, it is noteworthy that it has been shown that ethanol, which was ). The preparation of SMP was performed as described in [109]. All activities for SMP were measured in buffer containing 250 mM sucrose, 1 mM EDTA, 20 mM triethanolamine, 2.5 mM KCN and 2 mM NaN 3 (pH 7.4, 251C).…”