Abstract
PEX genes encode proteins (peroxins) that are required for the biogenesis of peroxisomes. One of these peroxins, Pex5p, is the receptor for matrix proteins with a type 1 peroxisomal targeting signal (PTS1), which shuttles newly synthesized proteins from the cytosol into the peroxisome matrix. We observed that in various Saccharomyces cerevisiae pex mutants disturbed in the early stages of PTS1 import, the steady-state levels of Pex5p are enhanced relative to wild type controls. Furthermore, we identified ubiquitinated forms of Pex5p in deletion mutants of those PEX genes that have been implicated in recycling of Pex5p from the peroxisomal membrane into the cytosol. Pex5p ubiquitination required the presence of the ubiquitin-conjugating enzyme Ubc4p and the peroxins that are required during early stages of PTS1 protein import. Finally, we provide evidence that the proteasome is involved in the turnover of Pex5p in wild type yeast cells, a process that requires Ubc4p and occurs at the peroxisomal membrane. Our data suggest that during receptor recycling a portion of Pex5p becomes ubiquitinated and degraded by the proteasome. We propose that this process represents a conserved quality control mechanism in peroxisome biogenesis.
Highlights
Peroxisomes are vital cell organelles and may contain highly variable sets of enzymes that control many important cellular processes
We describe the identification of ubiquitinated forms of Pex5p in mutants of PEX genes that encode two groups of physically interacting proteins (Pex4p/Pex22p and Pex1p/ Pex6p/Pex15p)
The identification of ubiquitinated Pex5p in a specific set of S. cerevisiae pex mutants and its dependence on other PEX genes is consistent with the role ascribed to certain peroxins in peroxisome biogenesis [2]
Summary
Peroxisomes are vital cell organelles and may contain highly variable sets of enzymes that control many important cellular processes. Peroxisomal enzymes are synthesized in the cytosol and delivered post-translationally to their target organelle To enable this sorting, these enzymes contain specific peroxisomal targeting signals (PTS), most of which fall into two categories (reviewed in Ref. 2). For both peroxisomal targeting signals, separate cytosolic receptor molecules have been discovered, Pex5p for the PTS1, and Pex7p for the PTS2 (reviewed in Ref. 2), which appear to have a shuttling function. The intraperoxisomal peroxin Pex8p, which has so far only been discovered in yeast species, appears to have a more direct role in matrix protein import by releasing PTS1-carrying cargo from Pex5p molecules [14, 15]. In Saccharomyces cerevisiae, these ATPases are bound to the peroxisomal membrane by a
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