Fatty acid beta-oxidation in peroxisomes and mitochondria: the first, unequivocal evidence for the involvement of carnitine in shuttling propionyl-CoA from peroxisomes to mitochondria.

We have investigated how [1-14C]propionyl-CoA, which is the first product of the peroxisomal beta-oxidation of [1-14C] pristanic acid, is transported to mitochondria for further oxidation in human skin fibroblasts from patients with a defect in the mitochondrial carnitine/acylcarnitine translocase and carnitine-palmitoyltransferase II (CPT II) (EC 2.3.1.21), respectively. Oxidation of pristanic acid was found to be partially deficient in both types of mutant cells. More important, 14CO2 production was completely deficient in the carnitine/acylcarnitine translocase deficient cells but not in the carnitine-palmitoyltransferase II deficient cells. These results strongly suggest that formation of 14CO2 in the Krebs cycle from [1-14C]propionyl-CoA as generated in peroxisomes requires the active participation of the mitochondrial carnitine/acylcarnitine translocase. The results described in this paper provide the first evidence suggesting that propionyl-CoA leaves the peroxisome as a carnitine ester and strongly suggest that the commonly accepted concept that peroxisomal beta-oxidation is not dependent on carnitine is incorrect.