Cofactor treatment improves ATP synthetic capacity in patients with oxidative phosphorylation disorders

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• 作者：Marriage ; Barbara J. ; Clandinin ; M. Thomas ; Macdonald ; Ian M. ; Glerum ; D. Moira
• 关键词：Mitochondrial disease ; Oxidative phosphorylation ; ATP ; Coenzyme Q₁₀
• 刊名：Molecular Genetics and Metabolism
• 出版年：2004
• 出版时间：April, 2004
• 年：2004
• 卷：81
• 期：4
• 页码：263-272
• 全文大小：391 K

文摘

Marked progress has been made over the past 15 years in defining the specific biochemical defects and underlying molecular mechanisms of oxidative phosphorylation disorders, but limited information is currently available on the development and evaluation of effective treatment approaches. Metabolic therapies that have been reported to produce a positive effect include coenzyme Q₁₀ (ubiquinone), other antioxidants such as ascorbic acid and vitamin E, riboflavin, thiamine, niacin, vitamin K (phylloquinone and menadione), and carnitine. The goal of these therapies is to increase mitochondrial ATP production, and to slow or arrest the progression of clinical symptoms. In the present study, we demonstrate for the first time that there is a significant increase in ATP synthetic capacity in lymphocytes from patients undergoing cofactor treatment. We also examined in vitro cofactor supplementation in control lymphocytes in order to determine the effect of the individual components of the cofactor treatment on ATP synthesis. A dose-dependent increase in ATP synthesis with CoQ₁₀ incubation was demonstrated, which supports the proposal that CoQ₁₀ may have a beneficial effect in the treatment of oxidative phosphorylation (OXPHOS) disorders.