The essential features of peroxisome biogenesis have been elucidated in recent years. These features are: 1) peroxisomes are not autonomously multiplying organelles but are derived from the endoplasmic reticulum; 2) all peroxisomal proteins, including peroxisomal matrix and membrane proteins, are encoded by the nuclear genome and synthesized on free polyribosomes; 3) the newly synthesized proteins are post-translationally imported from the cytosol into preexisting peroxisomes; and 4) import of new peroxisomal proteins into peroxisomes leads to an expansion of the size of peroxisomes, which makes them grow until a critical size is reached. Subsequently, the peroxisomes divide into two daughter peroxisomes that can then undergo the same cycle of events. Figure 24-1 presents a simplified scheme of peroxisome biogenesis. Correct targeting of proteins to peroxisomes is achieved via so-called peroxisome targeting signals (PTSs). Peroxisomal matrix proteins are targeted to peroxisomes via one of two different targeting signals which are short, conserved stretches of amino acids at the C-terminal (PTS1) or N-terminal (PTS2) end of peroxisomal matrix proteins. Several relevant proteins that possess PTS1 or PTS2 proteins are listed in Table 24-1. Proteins with PTS sequences are recognized in the cytosol by receptor proteins. The loaded receptors are then recognized specifically by the peroxisomal protein import machinery, after which the matrix proteins are translocated across the peroxisomal membrane, whereas the receptors are released back into the cytosol for another round of import. In principle, peroxisomal membrane proteins follow a similar pathway, although the targeting signal is different as well as the receptor recognizing this signal (Figure 24-1).
Model for the import of peroxisomal matrix proteins into human peroxisomes: Peroxisomal proteins are synthesized on free polyribosomes and contain one of two different peroxisome targeting signals (PTS1 and PTS2). PTS1 proteins are recognized in the cytosol by the cycling PTS1 receptor PEX5 which occurs in two different forms including a short form, PEX5S (5S in figure) and a long form, PEX5L (5L in figure). PEX5S is specifically involved in the import of PTS1-proteins whereas PEX5L is involved in the import of PTS2-proteins by forming a complex in the cytosol with PEX7, which binds PTS2-proteins. The PEX5S/PTS1-protein and PEX5L/PTS2-protein/PEX7 complexes dock specifically to the peroxisomal membrane by binding to the PEX13/PEX14 complex in the peroxisomal membrane. Subsequently, translocation of the two receptor-ligand complexes including: (1) the PEX5S/PTS1-protein complex and (2) the PEX5L/PTS2-protein/PEX7 complex followed by release of the PTS1- and PTS2-proteins into the peroxisomal matrix, occurs with the aid of the PEX2/ PEX10/PEX12 ring finger complex. Finally, the receptors PEX5S, PEX5L, and PEX7 are recycled back into the cytosol via the PEX1/PEX6/PEX26 complex.
TABLE 24-1Peroxisomal Enzyme Proteins from Humans and Their Peroxisomal Targeting Sequences (PTS1 AND PTS2) ||Download (.pdf) TABLE 24-1 Peroxisomal Enzyme Proteins from Humans and Their Peroxisomal Targeting Sequences (PTS1 AND PTS2)