Peroxisome matrix and membrane protein biogenesis

Abstract

Peroxisomes play an important role in lipid metabolic pathways and are implicated in many human disorders. Their biogenesis has been studied over the last two decades using many uni and multi-cellular model systems and many aspects of the mechanisms and proteins involved in peroxisome biogenesis are conserved from yeast to humans. In this manuscript we review the recent progress made in our understanding of the mechanisms by which matrix and membrane proteins are sorted to and assembled into peroxisomes.

Figure 1. The import of peroxisomal matrix proteins

(1) Cargoes are bound by a soluble receptor/s (Pex5 for PTS1 cargoes, Pex7 and PTS2 co-receptors for PTS2 cargoes, not depicted). (2) The receptor-cargo complex docks at the peroxisome membrane with the docking subcomplex. (3) The translocon is assembled and the receptor-cargo complex translocates into the peroxisome matrix. (4) The receptor-cargo complex is disassembled in the peroxisome matrix, causing cargo release. (5) Receptors are exported to the peroxisome membrane. (6a) Receptors are mono-ubiquitinated by Pex4 (for recycling) or (6b) poly-ubiquitinated by ubc4/5 (for degradation by the RADAR pathway). (7a) Receptors are recycled to the cytosol by the action of the AAA ATPases, Pex1 and Pex6, or (7b) degraded via the RADAR pathway involving the proteasome. (8) Receptors are deubiquitinated and utilized for the next round of import.