Peroxisome assembly and peroxisome biogenesis disorders

Abstract

Peroxisome biogenesis in mammals requires more than 15 genes. Two isoforms of the peroxisome targeting signal type 1 (PTS1) receptor, Pex5pS and Pex5pL, are identified in mammals. Pex5pS and Pex5pL bind PTS1 proteins. Pex5pL, but not Pex5pS, directly interacts with the PTS2 receptor, Pex7p, carrying its cargo PTS2 protein in the cytosol. Pex5p carrying the cargoes, PTS1 and PTS2, docks with the initial site Pex14p in a putative import machinery, subsequently unloads the cargoes and translocates to other components such as Pex13p, Pex2p, Pex10p, and Pex12p. The peroxins, Pex3p, Pex16p and Pex19p, function in the assembly of peroxisomal membrane vesicles that precedes the import of matrix proteins. Hence, peroxisomes may form de novo and do not have to arise from pre-existing, morphologically recognizable peroxisomes. Impaired peroxisome assembly causes peroxisome biogenesis disorders such as Zellweger syndrome of 12 complementation groups. Eleven pathogenic PEX genes have been isolated.