Mitochondrial oxidation of phytanic acid in human and monkey liver: implication that Refsum's disease is not a peroxisomal disorder.

The subcellular site of oxidation of [1-14C]phytanic acid to 14CO2 was investigated in human and monkey liver. In both species, this activity was associated with fractions enriched in mitochondria. Fractions enriched in peroxisomes had no detectable phytanic acid oxidase activity. The mitochondrial inhibitors antimycin A and rotenone significantly decreased 14CO2 production in mitochondria-rich fractions from human and monkey liver. These inhibitors also blocked phytanic acid oxidation in cultured human skin fibroblasts. These data suggest that alpha-oxidation of phytanic acid is a mitochondrial rather than a peroxisomal process in primates.