title: Contribution of peroxisome-specific isoform of Lon protease in sorting PTS1 proteins to peroxisomes.
abstract: Using an organelle proteomics approach, we previously studied the rat peroxisome in order to characterize the proteins participating in its biogenesis. A peroxisome-specific isoform of Lon (pLon) protein was accordingly identified. However, the precise role of pLon in peroxisomes remains to be elucidated. Here, we demonstrate that pLon plays a role in processing and activating a specific regulatory protein belonging to the peroxisome targeting signal (PTS) 1-containing proteins. Proteomic analysis of proteins co-immunoprecipitated with Lon suggested that Lon interacts with PMP70 and several enzymes involved in beta-oxidation, including acyl-CoA oxidase (AOX). The processing of AOX for its activation in peroxisomes was strongly inhibited in cells expressing a dominant negative form of pLon. Furthermore, a catalase possessing a modified PTS1 sequence was misdistributed in this cell line. pLon exhibits little, if any, in vitro AOX processing activity, and does not process PTS2-containing 3-ketoacyl-coenzyme A thiolase (PTL). Therefore, pLon may specifically control, sort and process PTS1 proteins. Based on the relationship between pLon and the beta-oxidation enzymes that regulate peroxisomal morphology, the observation of enlarged peroxisomes in cells expressing recombinant pLon suggests that pLon is a critical factor determining peroxisome morphology.
authors.affiliation: Institute for Enzyme Research, The University of Tokushima, Tokushima 770-8503, Japan.
authors.forename: Sizue
authors.initials: S
authors.lastname: Omi
authors.forename: Rie
authors.initials: R
authors.lastname: Nakata
authors.forename: Kazuko
authors.initials: K
authors.lastname: Okamura-Ikeda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Konishi
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Taniguchi
mesh_terms: D042962:Acyl-CoA Oxidase / Q000378:metabolism; D002374:Catalase / Q000032:analysis; D002460:Cell Line; D004798:Enzymes / Q000378:metabolism; D006801:Humans; D020675:Peroxisomes / Q000201:enzymology* / Q000648:ultrastructure; D049070:Protease La / Q000737:chemistry / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D021382:Protein Sorting Signals; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism
chemical_list: D004798:Enzymes; D020033:Protein Isoforms; D021382:Protein Sorting Signals; D011506:Proteins; D002374:Catalase; D042962:Acyl-CoA Oxidase; D049070:Protease La