The biogenesis of peroxisomes requires a group of protein factors referred to as peroxins which are encoded by the PEX genes. Peroxisomal proteins are synthesized on free polyribosomes and imported posttranslationally. The transport of peroxisomal matrix proteins from the cytoplasm to the peroxisome is mediated by two peroxisome-targeting signal sequences (PTS1 and PTS2). Peroxisomal membrane proteins (PMPs) are imported independently of the matrix proteins by a distinct mechanism mediated by the membrane PTS signal (mPTS) (3, 6, 7, 8 and references therein).

In yeast, Pex19p and Pex3p are two proteins required for the proper localization and stability of PMPs (3). Pex3p is a peroxisomal membrane protein and is targeted to the peroxisome via the ER (2, 4). Pex3p first localizes in the ER as small dot like ER substructures before reaching the peroxisomes. Pex19p is required for the exit of Pex3p from the ER (9, 10, 11). The N-terminal region of Pex3p contains its peroxisomal targeting signal (11). pex3 null mutants completely lack detectable peroxisomal membrane structures and mislocalize the PMPs to the cytosol where they are rapidly degraded (3).

PEX3 is evolutionarily conserved,and shares sequence similarity with human PEX3. The human peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous diseases characterized by severe mental retardation, neuronal, hepatic and renal abnormalities, and death in early infancy. Mutations in human PEX3 have been associated with Zellweger Syndrome and Refsum Disease (12).

Last updated: 2007-07-05