The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript.
Lithium-induced enhancement of mitochondrial oxidative phosphorylation in human brain tissue
Article first published online: 10 JUL 2009
© 2009 The Authors. Journal compilation © 2009 John Wiley & Sons A/S
Volume 11, Issue 5, pages 515–522, August 2009
How to Cite
Maurer, I. C., Schippel, P. and Volz, H.-P. (2009), Lithium-induced enhancement of mitochondrial oxidative phosphorylation in human brain tissue. Bipolar Disorders, 11: 515–522. doi: 10.1111/j.1399-5618.2009.00729.x
- Issue published online: 10 JUL 2009
- Article first published online: 10 JUL 2009
- Received 24 September 2008, revised and accepted for publication 10 February 2009
- bipolar disorder;
- complex I;
- respiratory chain
Objectives: Extensive preclinical and clinical evidence suggests mitochondrial dysfunction in bipolar disorder. Studies of brain energy metabolism in bipolar disorder suggest an impairment of energy generation by mitochondrial oxidative phosphorylation. Lithium is an effective drug widely used in treating bipolar disorder, but its mechanism of action has remained uncertain. The aim of this study was to clarify the effect of lithium on mitochondrial oxidative phosphorylation.
Methods: We spectrophotometrically determined the activities of the respiratory chain complexes I + III [antimycin A-sensitive nicotinamide adenine dinucleotide (NADH) cytochrome c oxidorductase], complexes II + III (succinate cytochrome c oxidoreductase), succinate dehydrogenase, and complex IV [cytochrome c oxidase (COX)], and of the mitochondrial matrix enzyme citrate synthase in postmortem human brain cortex homogenates following exposure to lithium (up to 10 mM).
Results: Activities of complexes I + III and of complexes II + III were dose-dependently increased by lithium with maximum values at 1 mM (165%, p = 0.03, and 146%, p = 0.00002, of controls). Activity of succinate dehydrogenase remained unchanged up to 2 mM, but was raised at higher drug concentrations (maximum 220%, p = 0.01, of controls). In contrast, activity of COX was not significantly affected by the drug (decrease of 12% at 1 mM, p = 0.4).
Conclusions: Our study suggests that lithium stimulates mitochondrial respiratory chain enzyme activities at clinically relevant concentrations. Lithium’s effect on the mitochondrial respiratory chain presents further evidence of the pathophysiological significance of mitochondrial dysfunction in bipolar disorder. The effect may be relevant to the therapeutic efficacy of the drug by potentially reversing a disease-related alteration.