The AAA peroxins, Pex1p and Pex6p, are components of the peroxisomal protein import machinery required for the relocation of the import receptor Pex5p from the peroxisomal membrane to the cytosol. We demonstrate that Pex1p and Pex6p form a stable complex in the cytosol, which associates at the peroxisomal membrane with their membrane anchor Pex15p and the peroxisomal importomer. The interconnection of Pex15p with the components of the importomer was independent of Pex1p and Pex6p, indicating that Pex15p is an incorporated component of the assembly. Further evidence suggests that the AAA peroxins shuttle between cytosol and peroxisome with proper binding of the Pex15p-AAA complex to the importomer and release of the AAA peroxins from the peroxisomal membrane depending on an operative peroxisomal protein import mechanism. Pex4p-deficient cells exhibit a wild-type-like assembly of the importomer, which differs in that it is associated with increased amounts of Pex1p and Pex6p, in agreement with a function for Pex4p in the release of AAA peroxins from the peroxisomal membrane.
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http://dx.doi.org/10.1111/j.1742-4658.2006.05388.x | DOI Listing |
Annu Rev Biochem
August 2024
Systembiochemie, Ruhr-Universität Bochum, Bochum, Germany.
Front Cell Infect Microbiol
March 2024
Department of Systems Biochemistry, Faculty of Medicine, Institute for Biochemistry and Pathobiochemistry, Ruhr University Bochum, Bochum, Germany.
Trypanosomatid parasites are kinetoplastid protists that compartmentalize glycolytic enzymes in unique peroxisome-related organelles called glycosomes. The heterohexameric AAA-ATPase complex of PEX1-PEX6 is anchored to the peroxisomal membrane and functions in the export of matrix protein import receptor PEX5 from the peroxisomal membrane. Defects in PEX1, PEX6 or their membrane anchor causes dysfunction of peroxisomal matrix protein import cycle.
View Article and Find Full Text PDFMethods Mol Biol
April 2023
Interfaculty Institute of Biochemistry (IFIB), Cell Biochemistry, University of Tuebingen, Tuebingen, Germany.
The heteromeric complex of the two AAA+ ATPases PEX1 and PEX6 is involved in the export of the monoubiquitinated import receptor PEX5 from the peroxisomal membrane. Mutations in this complex make up for over 60% of the patients with Peroxisomal Biogenesis Disorders. To have better options for the treatment of the milder mutations we purified the human PEX1/PEX6 complex after overexpression of plasmids encoding tagged proteins from HEK293TT cells.
View Article and Find Full Text PDFJ Mol Biol
January 2023
Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal. Electronic address:
The AAA ATPases PEX1•PEX6 extract PEX5, the peroxisomal protein shuttling receptor, from the peroxisomal membrane so that a new protein transport cycle can start. Extraction requires ubiquitination of PEX5 at residue 11 and involves a threading mechanism, but how exactly this occurs is unclear. We used a cell-free in vitro system and a variety of engineered PEX5 and ubiquitin molecules to challenge the extraction machinery.
View Article and Find Full Text PDFElife
April 2022
Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States.
Autophagy receptor (or adaptor) proteins facilitate lysosomal destruction of various organelles in response to cellular stress, including nutrient deprivation. To what extent membrane-resident autophagy receptors also respond to organelle-restricted cues to induce selective autophagy remains poorly understood. We find that latent activation of the yeast pexophagy receptor Atg36 by the casein kinase Hrr25 in rich media is repressed by the ATPase activity of Pex1/6, the catalytic subunits of the exportomer AAA+ transmembrane complex enabling protein import into peroxisomes.
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