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Published on: July 7, 2013
Effect of resveratrol on cultured skin fibroblasts from patients with oxidative phosphorylation defects
Boel De Paepe1, Katrien Vandemeulebroecke, Joél Smet
1Department of Pediatrics, Division of Pediatric Neurology and Metabolism, Ghent University Hospital, Ghent, Belgium.
Abstract:
Few therapeutic options are available to patients with oxidative phosphorylation disorders. Administering pharmacological agents that are able to stimulate mitochondrial biogenesis have been put forward as a possible treatment, yet the approach remains in need of thorough testing. We investigated the effect of resveratrol in an in vitro setting. Mitochondrial enzymatic activities were tested in cultured skin fibroblasts from patients harboring a nuclear defect in either complex II or complex IV (n = 11), and in fibroblasts from healthy controls (n = 11). In the latter, preincubation with resveratrol resulted in a significant increase of citrate synthase, complex II and complex IV enzyme activity. In patients with complex II or complex IV deficiency, however, activity of the deficient complex could not be substantially augmented, and response was dependent upon the residual activity. We conclude that resveratrol is not capable of normalizing oxidative phosphorylation activities in deficient cell lines.
Insights
Resveratrol did not normalize oxidative phosphorylation in patient cells, despite increasing mitochondrial enzymes in healthy controls. This suggests resveratrol is not a viable treatment for these specific mitochondrial disorders.
Area of Science:
- Biochemistry
- Cell Biology
- Genetics
Background:
- Oxidative phosphorylation disorders have limited treatment options.
- Stimulating mitochondrial biogenesis is a potential therapeutic strategy.
- Resveratrol's effects on mitochondrial function require further investigation.
Purpose of the Study:
- To investigate the in vitro effect of resveratrol on mitochondrial enzymatic activities.
- To assess resveratrol's potential to improve function in cells with oxidative phosphorylation defects.
Main Methods:
- Cultured skin fibroblasts from patients with complex II or IV nuclear defects (n=11) and healthy controls (n=11) were used.
- Mitochondrial enzymatic activities, including citrate synthase, complex II, and complex IV, were measured.
- Fibroblasts were preincubated with resveratrol.
Main Results:
- Resveratrol significantly increased citrate synthase, complex II, and complex IV activity in healthy control fibroblasts.
- In patient fibroblasts with complex II or IV deficiency, resveratrol did not substantially augment the activity of the deficient complex.
- The response in patient cells was dependent on the residual enzyme activity.
Conclusions:
- Resveratrol does not normalize oxidative phosphorylation activities in cell lines with complex II or IV deficiency.
- The therapeutic potential of resveratrol for these specific mitochondrial disorders is limited.
- Further research is needed to identify effective treatments for oxidative phosphorylation disorders.
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