Import and quality control of peroxisomal proteins

Abstract

Peroxisomes are involved in a multitude of metabolic and catabolic pathways, as well as the innate immune system. Their dysfunction is linked to severe peroxisome-specific diseases, as well as cancer and neurodegenerative diseases. To ensure the ability of peroxisomes to fulfill their many roles in the organism, more than 100 different proteins are post-translationally imported into the peroxisomal membrane and matrix, and their functionality must be closely monitored. In this Review, we briefly discuss the import of peroxisomal membrane proteins, and we emphasize an updated view of both classical and alternative peroxisomal matrix protein import pathways. We highlight different quality control pathways that ensure the degradation of dysfunctional peroxisomal proteins. Finally, we compare peroxisomal matrix protein import with other systems that transport folded proteins across membranes, in particular the twin-arginine translocation (Tat) system and the nuclear pore.

The peroxisome: an update on mysteries 3.0

“…Most of the mammalian cargo proteins contain a PTS1 at the very C-terminus, explaining why the proteins need to be imported post-translationally. The “transient pore” model postulates that the PEX5-cargo complex inserts into the peroxisomal membrane and initiates the formation of a large pore for cargo translation, which is however short-lived in nature (Erdmann and Schliebs 2005 ; Meinecke et al 2010 ; Walter and Erdmann 2019 ; Blum et al 2023 ; Rudowitz and Erdmann 2023 ) (Fig. 1 top).…”

“…Furthermore, PEX13 contains a series of conserved Tyr-Gly (YG) repeats within its own IDR. Interestingly, the IDRs resemble those of nucleoporin proteins of nuclear pore complexes (e.g., the nucleoporin FG repeats), suggesting similarities of peroxisomal protein import to nuclear transport, with PEX5 acting as a shuttling receptor analogously to karyopherins (Barros-Barbosa et al 2019 ; Gao et al 2022 ; Ravindran et al 2023 ; Rudowitz and Erdmann 2023 ). In line with this, purified YG domains were shown to form hydrogels into which PEX5 selectively partitions, using conserved aromatic WxxxF/Y motifs.…”

Editorial: Targeting signals in protein trafficking and transport

“…Peroxisomes are single membrane bound organelles with two types of peroxisomal targeting signals for matrix proteins (PTS1 and PTS2) and another for peroxisomal membrane proteins (mPTS), which are recognized by the receptor proteins PEX5, PEX7 together with a co-receptor, and PEX19, respectively ( Rudowitz and Erdmann, 2023 ). Krishna et al describe targeting signals encoded in the peroxisomal membrane protein PEX11 from the protozoon Trypanosoma brucei , which not only has binding sites for the cognate peroxisomal receptor PEX19 but also for the mitochondrial receptor TOM20 although mitochondrial targeting is only observed when no peroxisomes are present.…”

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Editorial on the Research Topic Targeting signals in protein trafficking and transport "This Research Topic of Frontiers in Physiology is dedicated to the memory of Professor Anastassios (Tassos) Economou, one of the guest editors of this issue, who recently passed away during its formation. "

PeroxisomesPeroxisomes are single membrane bound organelles with two types of peroxisomal targeting signals for matrix proteins (PTS1 and PTS2) and another for peroxisomal membrane proteins (mPTS), which are recognized by the receptor proteins PEX5, PEX7 together with a co-receptor, and PEX19, respectively (Rudowitz and Erdmann, 2023). Krishna et al describe targeting signals encoded in the peroxisomal membrane protein PEX11 from the protozoon Trypanosoma brucei, which not only has binding sites for the cognate peroxisomal receptor PEX19 but also for the mitochondrial receptor

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