Protein transport into peroxisomes: Knowns and unknowns

• Published in: BioEssays Vol. 39; no. 10
• Main Authors: Francisco, Tânia, Rodrigues, Tony A., Dias, Ana F., Barros‐Barbosa, Aurora, Bicho, Diana, Azevedo, Jorge E.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.10.2017
• Subjects: Animals; Cytosol; Humans; peroxisomal import machinery; Peroxisomal Targeting Signal 2 Receptor - metabolism; Peroxisome-Targeting Signal 1 Receptor - metabolism; Peroxisomes; Peroxisomes - metabolism; PEX5; PEX7; protein import; protein translocation; Protein transport; Protein Transport - physiology; Proteins; Ribosomes; Signal Transduction - physiology; Synthesis; Ubiquitination; Ubiquitination - physiology; peroxisomal import machinery; PEX7; peroxisomes; protein import; PEX5; protein translocation
• ISSN: 0265-9247; 1521-1878
• DOI: 10.1002/bies.201700047

Peroxisomal matrix proteins are synthesized on cytosolic ribosomes and rapidly transported into the organelle by a complex machinery. The data gathered in recent years suggest that this machinery operates through a syringe‐like mechanism, in which the shuttling receptor PEX5 − the “plunger” − pushes a newly synthesized protein all the way through a peroxisomal transmembrane protein complex − the “barrel” − into the matrix of the organelle. Notably, insertion of cargo‐loaded receptor into the “barrel” is an ATP‐independent process, whereas extraction of the receptor back into the cytosol requires its monoubiquitination and the action of ATP‐dependent mechanoenzymes. Here, we review the main data behind this model. The peroxin PEX5 is the peroxisomal matrix protein receptor. It shuttles between the cytosol and the organelle membrane, where it gets inserted into the docking/translocation module, thus pushing the cargo‐protein into the peroxisome lumen. Resetting the system involves PEX5 monoubiquitination and its extraction from the membrane by the AAA‐ATPases, PEX1/PEX6.