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Review
. 2013 Sep 24:4:261.
doi: 10.3389/fphys.2013.00261.

Import of proteins into the peroxisomal matrix

Affiliations
Review

Import of proteins into the peroxisomal matrix

Sohel Hasan et al. Front Physiol. .

Abstract

Peroxisomes constitute a dynamic compartment in all nucleated cells. They fulfill diverse metabolic tasks in response to environmental changes and cellular demands. This adaptation is implemented by modulation of the enzyme content of the organelles, which is accomplished by dynamically operating peroxisomal protein transport machineries. Soluble import receptors recognize their newly synthesized cargo proteins in the cytosol and ferry them to the peroxisomal membrane. Subsequently, the cargo is translocated into the matrix, where the receptor is ubiquitinated and exported back to the cytosol for further rounds of matrix protein import. This review discusses the recent progress in our understanding of the peroxisomal matrix protein import and its regulation by ubiquitination events as well as the current view on the translocation mechanism of folded proteins into peroxisomes. This article is part of a Special Issue entitled: Origin and spatiotemporal dynamics of the peroxisomal endomembrane system.

Keywords: biogenesis; peroxisome; protein import; targeting; translocation; ubiquitination.

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Figures

Figure 1
Figure 1
Matrix protein import into peroxisomes. Most principles of peroxisomal protein import are evolutionary conserved. The schematic representation shown here refers to the situation in Saccharomyces cerevisiae. Peroxisomal matrix protein import takes place posttranslationally and requires an elaborate protein import machinery, consisting of peroxisome biogenesis factors, so called peroxins. (A) Another feature of peroxisomal import is the requirement for cycling receptors. The import process can conceptually be divided into cargo-recognition by the receptors in the cytosol, docking of the receptor/cargo-complex at the peroxisomal membrane, cargo translocation and finally export of the receptor back to the cytosol. (B) Cargo-recognition and docking: Proteins harboring a peroxisomal targeting signal of type 1 (PTS1) or type II (PTS2) are recognized in the cytosol by specific import receptors, Pex5p and Pex7p, respectively. Alternatively, some cargo proteins do not harbor a PTS or do not essential depend on it. Some of these non-PTS proteins (nPTS) bind to the N-terminus of Pex5p or to canonical PTS1-proteins. The cargo-loaded receptors are directed to a docking complex at the peroxisomal membrane. For this, the PTS2-receptor Pex7p requires auxiliary proteins, in baker's yeast these are the redundant Pex18p or Pex21p. The receptor-cargo-complexes bind to the docking-complex (Pex13p, Pex14p and Pex17p) at the peroxisomal membrane. The following steps are better known for the PTS1- than the PTS2-pathway. (C) Cargo-translocation: It is assumed that the association of Pex14p and cargo-loaded Pex5p leads to the formation of a transient pore, which functions as a protein-conducting channel. The cargo is translocated into the peroxisomal lumen in an unknown manner. In intraperoxisomal Pex8p, a pH-shift or the redox-state might be involved in receptor-cargo dissociation. (D) At the end of the import cascade, the receptor is recycled from the peroxisomal membrane back to the cytosol for another round of import. For this, Pex5p is monoubiquitinated by the Pex22p-anchored ubiquitin-conjugating enzyme Pex4p and the ubiquitin-protein ligase Pex12p, which forms the RING-finger complex together with the other ubiquitin-protein ligases Pex2p and Pex10p. Pex5p-polyubiquitination is performed by the ubiquitin-conjugating enzyme Ubc4p in conjunction with the ubiquitin-protein ligases Pex2p and Pex10p. For Pex5p, it has been demonstrated that the ubiquitin-signal leads to an ATP-dependent dislocation of Pex5p from the peroxisomal membrane. This process is performed by the AAA-type ATPases Pex1p and Pex6p, which are anchored to the peroxisomal membrane via Pex15p. During or shortly after receptor export to the cytosol, the ubiquitin is removed by the ubiquitin-hydrolase Ubp15p.

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References

    1. Agne B., Meindl N. M., Niederhoff K., Einwächter H., Rehling P., Sickmann A., et al. (2003). Pex8p. An intraperoxisomal organizer of the peroxisomal import machinery. Mol. Cell 11, 635–646 10.1016/S1097-2765(03)00062-5 - DOI - PubMed
    1. Albiniak A. M., Baglieri J., Robinson C. (2012). Targeting of lumenal proteins across the thylakoid membrane. J. Exp. Bot. 63, 1689–1698 10.1093/jxb/err444 - DOI - PubMed
    1. Alencastre I. S., Rodrigues T. A., Grou C. P., Fransen M., Sá-Miranda C., Azevedo J. E. (2009). Mapping the cargo protein membrane translocation step into the PEX5 cycling pathway. J. Biol. Chem. 284, 27243–27251 10.1074/jbc.M109.032565 - DOI - PMC - PubMed
    1. Amerik A. Y., Hochstrasser M. (2004). Mechanism and function of deubiquitinating enzymes. Biochim. Biophys. Acta 1695, 189–207 10.1016/j.bbamcr.2004.10.003 - DOI - PubMed
    1. Azevedo J. E., Schliebs W. (2006). Pex14p, more than just a docking protein. Biochim. Biophys. Acta 1763, 1574–1584 10.1016/j.bbamcr.2006.09.002 - DOI - PubMed

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