[Molecular biology of peroxisome biogenesis]

Molecular mechanisms of peroxisomal protein translocation and peroxisome assembly have been extensively studied these several years. One type of topogenic signals has been identified both in vivo and in vitro: the C-terminal -Ser-Lys-Leu-COOH (SKL) motif sequence. In patients with generalized peroxisomal disease such as autosomal recessive, cerebrohepatorenal Zellweger syndrome where peroxisomes are morphologically absent, all peroxisomal proteins appear to be normally synthesized but assembly of peroxisomes is impaired. We have isolated several somatic animal cell mutants defective in biogenesis of peroxisomes. By genetic complementation analysis following the transfection of cDNA library to a CHO cell mutant, Z65, we cloned a cNDA for 35-kDa peroxisome assembly factor-1 (PAF-1) essential for peroxisome assembly. Furthermore, we have recently delineated the primary defect in a Zellweger patient who belonged to the same complementation group as the Z65. The cause of this syndrome was a homozygous nonsense point mutation in the PAF-1 gene.