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Antioxidant and prooxidant properties of mitochondrial Coenzyme Q

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Abstract

Coenzyme Q is both an essential electron carrier and an important antioxidant in the mitochondrial inner membrane. The reduced form, ubiquinol, decreases lipid peroxidation directly by acting as a chain breaking antioxidant and indirectly by recycling Vitamin E. The ubiquinone formed in preventing oxidative damage is reduced back to ubiquinol by the respiratory chain. As well as preventing lipid peroxidation, Coenzyme Q reacts with other reactive oxygen species, contributing to its effectiveness as an antioxidant. There is growing interest in using Coenzyme Q and related compounds therapeutically because mitochondrial oxidative damage contributes to degenerative diseases. Paradoxically, Coenzyme Q is also involved in superoxide production by the respiratory chain. To help understand how Coenzyme Q contributes to both mitochondrial oxidative damage and antioxidant defences, we have reviewed its antioxidant and prooxidant properties.

Section snippets

Hydrophobicity of Coenzyme Q

CoQ consists of a quinoid head group attached to a long, hydrophobic tail of 6 (Saccharomyces cerevisiae), 8 (Escherichia coli), 9 (rodent) or 10 (human) 5-carbon isoprene units (Fig. 1). The predominant redox forms of CoQ are the oxidised ubiquinone (UQ) and the reduced ubiquinol (UQH2). UQ is reduced to UQH2 by addition of two electrons and two protons by ubiquinone reductases (Fig. 1). The quinoid head groups of both molecules are more polar than their isoprene chains, but still sufficiently

Lipid peroxidation

The major antioxidant role of CoQ is in preventing lipid peroxidation [6], [7]. Lipid peroxidation is a chain reaction initiated by abstraction of a hydrogen atom (Hradical dot) from the unsaturated fatty acids (LH) of a phospholipid by a radical such as the hydroxyl radical [27]LH+HO→L+H2OThe carbon centred radicals thus generated (Lradical dot) react rapidly with oxygen to form peroxyl radicals (LOOradical dot), which can abstract a further Hradical dot from an unsaturated fatty acid to generate a lipid peroxide, as well as further

Autoxidation of Coenzyme Q

UQH2 spontaneously autoxidises in the presence of oxygen by the overall reactionUQH2+O2→UQ+H2O2As the direct reaction between UQH2 and oxygen is negligible (Table 2), autoxidation is initiated by the following reactions of the ubiquinolate anion:UQH−+O2→UQ−+O2−+H+UQ−+O2→UQ+O2−The superoxide formed can then dismutate to hydrogen peroxide2O2−+2H+→H2O2+O2Because of this requirement for the ubiquinolate anion, autoxidation does not occur at pH 6 or below, is very slow below pH 8, and only becomes

Conclusion

The antioxidant role of mitochondrial CoQ is surprisingly complicated. Its ability to act as an antioxidant depends on all three redox forms, ubiquinone, the ubisemiquinone radical, and ubiquinol. Within the phospholipid bilayer UQH2 is the dominant antioxidant, preventing lipid peroxidation directly and through recycling Vitamin E. Thus, the redox state of the CoQ pool plays a critical role in preventing lipid peroxidation, as is illustrated in Fig. 3. CoQ is also a prooxidant under some

Acknowledgements

We thank Martin D. Brand, Telma Esteves, and Meredith F. Ross for helpful comments on the manuscript.

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