8.
Refsum disease is a rare, inherited neurodegenerative disorder characterized by accumulation of the dietary branched-chain
fatty acid phytanic acid in plasma and tissues caused by a defect in the alphaoxidation pathway. The accumulation of phytanic
acid is believed to be the main pathophysiological cause of the disease. However, the exact mechanism(s) by which phytanic
acid exerts its toxicity have not been resolved. In this study, the effect of phytanic acid on mitochondrial respiration was
investigated. The results show that in digitonin-permeabilized fibroblasts, phytanic acid decreases ATP synthesis, whereas
substrate oxidation
per se is not affected. Importantly, studies in intact fibroblasts revealed that phytanic acid decreases both the mitochondrial
membrane potential and NAD(P)H autofluorescence. Taken together, the results described here show that unesterified phytanic
acid exerts its toxic effect mainly through its protonophoric action, at least in human skin fibroblasts.
Received 4 August 2007; received after revision 26 September 2007; accepted 10 October 2007
J. C. Komen, F. Distelmaier: These authors contributed equally to this work.
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