title: The AAA peroxins Pex1p and Pex6p function as dislocases for the ubiquitinated peroxisomal import receptor Pex5p.
abstract: The discovery of the peroxisomal ATPase Pex1p triggered the beginning of the research on AAA (ATPase associated with various cellular activities) proteins and the genetic dissection of peroxisome biogenesis. Peroxisomes are virtually ubiquitous organelles, which are connected to diverse cellular functions. The highly diverse and adaptive character of peroxisomes is accomplished by modulation of their enzyme content, which is mediated by dynamically operating protein-import machineries. The import of matrix proteins into the peroxisomal lumen has been described as the ATP-consuming step, but the corresponding reaction, as well as the ATPase responsible, had been obscure for nearly 15 years. Recent work using yeast and human fibroblast cells has identified the peroxisomal AAA proteins Pex1p and Pex6p as mechano-enzymes and core components of a complex which dislocates the cycling import receptor Pex5p from the peroxisomal membrane back to the cytosol. This AAA-mediated process is regulated by the ubiquitination status of the receptor. Pex4p [Ubc10p (ubiquitin-conjugating enzyme 10)]-catalysed mono-ubiquitination of Pex5p primes the receptor for recycling, thereby enabling further rounds of matrix protein import, whereas Ubc4p-catalysed polyubiquitination targets Pex5p to proteasomal degradation.
authors.affiliation: Abteilung für Systembiochemie, Medizinische Fakultät der Ruhr-Universität Bochum, D-44780 Bochum, Germany.
authors.forename: Harald W
authors.initials: HW
authors.lastname: Platta
authors.forename: Mykhaylo O
authors.initials: MO
authors.lastname: Debelyy
authors.forename: Fouzi
authors.initials: F
authors.lastname: El Magraoui
authors.forename: Ralf
authors.initials: R
authors.lastname: Erdmann
mesh_terms: D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism*; D020675:Peroxisomes / Q000378:metabolism*; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D008666:Metalloendopeptidases; C114583:m-AAA proteases