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Review
. 2011 Apr 4;193(1):7-16.
doi: 10.1083/jcb.201010022.

Peroxisome assembly: matrix and membrane protein biogenesis

Changle Ma  1 , Gaurav Agrawal, Suresh Subramani
Affiliations
Review

Peroxisome assembly: matrix and membrane protein biogenesis

Changle Ma et al. J Cell Biol. .

Abstract

The biogenesis of peroxisomal matrix and membrane proteins is substantially different from the biogenesis of proteins of other subcellular compartments, such as mitochondria and chloroplasts, that are of endosymbiotic origin. Proteins are targeted to the peroxisome matrix through interactions between specific targeting sequences and receptor proteins, followed by protein translocation across the peroxisomal membrane. Recent advances have shed light on the nature of the peroxisomal translocon in matrix protein import and the molecular mechanisms of receptor recycling. Furthermore, the endoplasmic reticulum has been shown to play an important role in peroxisomal membrane protein biogenesis. Defining the molecular events in peroxisome assembly may enhance our understanding of the etiology of human peroxisome biogenesis disorders.

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Figures

Figure 1.
Figure 1.
The import of peroxisomal matrix proteins. The process may be divided into distinct steps (white numbers in closed black circles). Bold numbers indicate corresponding Pex proteins. The steps are: (1) Receptor–cargo interaction in the cytosol (PTS2 pathway is not depicted). (2) Receptor–cargo docking at the peroxisomal membrane with the docking subcomplex, inducing the assembly of the translocon. (3) Translocation of the receptor–cargo complex across the membrane followed by the dissociation of the receptor–cargo complex; i.e., cargo release. (4) Export of cargo-free receptors from the peroxisome matrix to the membrane. (5a) Monoubiquitination of the receptor on a cysteine by Pex4 and Pex2 (for receptor recycling) or (5b) polyubiquitination of the receptor on a lysine by Ubc4/5 and Pex10/12 (for degradation by the RADAR pathway). (6a) Receptor recycling from the peroxisome membrane back to the cytosol by the action of the AAA ATPases (Pex1 and Pex6) and ATP hydrolysis, or (6b) degradation of a receptor that is blocked from recycling via the RADAR pathway involving the proteasome. (7) Deubiquitination of the receptor before the next round of import. The squiggly line on Pex5 denotes its disordered N-terminal segment.
Figure 2.
Figure 2.
Contribution of the ER to peroxisome biogenesis. Most, if not all, PMPs are first imported into the ER through the Sec61/SSH1 translocon or the GET3 complex (left inset), are sorted into a pre-peroxisomal compartment, and bud out in a Pex3/Pex19-dependent manner to form pre-peroxisomal vesicles (right inset). These vesicles can form mature peroxisomes after fusion, dependent on Pex1/Pex6 (Titorenko and Rachubinski, 1998) and matrix protein import (de novo pathway). The de novo pathway repopulates cells with peroxisomes in the biogenesis mutants (e.g., pex3Δ/pex19Δ) lacking the organelle when corresponding genes are reintroduced (Elgersma et al., 1997; Fang et al., 2004; Tam et al., 2005; Hoepfner et al., 2005; Motley and Hettema, 2007; Motley et al., 2008; Perry et al., 2009; van der Zand et al., 2010). Alternatively, the pre-peroxisomal vesicles fuse with divided peroxisomes generated from preexisting mature peroxisomes. Peroxisome division requires Pex11 and a specific set of DRPs. In plants, retrograde trafficking from peroxisomes to the ER has been described (McCartney et al., 2005).
Figure 3.
Figure 3.
Alternative roles of Pex19 in the insertion of PMPs into the peroxisomal membrane. The role of Pex19 in peroxisome biogenesis and import of various PMPs has been clearly established in yeast and mammals, but its mechanism of action is still a matter of debate (Snyder et al., 1999; Sacksteder et al., 2000). Previous studies implicated Pex3 and Pex19 in the posttranslational insertion of PMPs. Pex19 serving as a chaperone binds and stabilizes newly synthesized mPTS-containing PMPs in the cytoplasm, and transports them to peroxisomes by docking to Pex3 present in the peroxisomal membrane (Muntau et al., 2003; Fang et al., 2004; Jones et al., 2004; Matsuzono and Fujiki, 2006; Matsuzono et al., 2006). However, subsequent studies in yeast show the requirement of Pex19 for the exit of most, if not all PMPs, including Pex3, from the ER (Fig. 2 B; Hoepfner et al., 2005; Lam et al., 2010; van der Zand et al., 2010; unpublished data). In the light of the Pex19-independent insertion of most PMPs into the ER and the role of Pex19 in mediating the budding of pre-peroxisomal vesicles, the role of Pex19 in the posttranslational import of PMPs is questionable for all PMPs that go to peroxisomes via the ER.
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