PEX1

PEX1 is a peroxisomal biogenesis factor (peroxin) encoded by the PEX1 gene in humans. It belongs to the family of AAA-ATPases and resides in the peroxisomal membrane, where it forms a complex with PEX6 and the adaptor protein PEX26. Together, the PEX1-PEX6-PEX26 complex drives ATP-dependent steps in peroxisome biogenesis and matrix protein import.

Within the peroxisomal import cycle, peroxisomal targeting signal (PTS1/PTS2) proteins are bound by the cytosolic receptor PEX5/PEX7 and delivered to the peroxisomal membrane via docking proteins such as PEX13/PEX14. After cargo release into the peroxisome, PEX5 is recycled back to the cytosol; this recycling requires ubiquitination and extraction by the PEX1-PEX6-PEX26 ATPase motor, which uses ATP hydrolysis to remove PEX5 from the membrane and prepare it for another round of import.

Mutations in PEX1 disrupt peroxisome assembly and matrix protein import, leading to peroxisomal biogenesis disorders. The most common PEX1-related conditions are Zellweger spectrum disorders, which range from severe neonatal forms to milder presentations such as infantile Refsum disease and Heimler syndrome in some cases. The clinical outcome depends on the nature of the mutation and residual peroxisome function.

Evolutionarily, PEX1 is highly conserved across eukaryotes with peroxisomes and operates in concert with PEX6; the PEX1-PEX6 complex is a hallmark of the peroxisomal import machinery. Abnormalities in this pathway affect the assembly of peroxisomes and the import of enzymes involved in fatty acid beta-oxidation and other metabolic processes.