ABSTRACT

Peroxisome biogenesis disorders (PBDs) are clinically classified into 3 phenotypes: Zellweger syndrome (ZS), the most severe; neonatal adrenoleukodystrophy (NALD), intermediate; and infantile Refsum disease (IRD), the mildest form. Cell fusion studies revealed that there are at least 12 complementation groups (CGs) in PBDs. Although responsible genes (PEXs) have been isolated for many CGs in PBDs, it remains clear about the metabolic and molecular bases of clinical phenotypes. We elucidated the temperature-sensitive (ts) formation of peroxisomes in the fibroblasts of milder forms of PBDs. Peroxisomal enzymes were normally localized into peroxisomes and biochemical functions of peroxisomes, including very-long chain fatty acids (VLCFA) oxidation and dihydroxyacetonphosphate-acyltransferase (DHAP-AT) activity, were restored after incubation for 72 hour at 30 °C. The ts phenomenon was caused by the ts mutations in each PEX genes, including PEX1, PEX2, PEX6 and PEX13. We also identified the characteristic ts import of acyl-CoA oxidase, the first enzyme of peroxisome beta-oxidation, in the fibroblasts from PBDs including ZS belonging to CG-A.