title: Acyl-CoA oxidase is imported as a heteropentameric, cofactor-containing complex into peroxisomes of Yarrowia lipolytica.
abstract: Five isoforms of acyl-CoA oxidase (Aox), designated Aox1p to Aox5p, constitute a 443-kD heteropentameric complex containing one polypeptide chain of each isoform within the peroxisomal matrix of the yeast Yarrowia lipolytica. Assembly of the Aox complex occurs in the cytosol and precedes its import into peroxisomes. Peroxisomal targeting of the Aox complex is abolished in a mutant lacking the peroxin Pex5p, a component of the matrix protein targeting machinery. Import of the Aox complex into peroxisomes does not involve the cytosolic chaperone Pex20p, which mediates the oligomerization and import of peroxisomal thiolase. Aox2p and Aox3p play a pivotal role in the formation of the Aox complex in the cytosol and can substitute for one another in promoting assembly of the complex. In vitro, these subunits retard disassembly of the Aox complex and increase the efficiency of its reassembly. Neither Aox2p nor Aox3p is required for acquisition of the cofactor FAD by other components of the complex. We provide evidence that the Aox2p- and Aox3p-assisted assembly of the Aox complex in the cytosol is mandatory for its import into peroxisomes and that no component of the complex can penetrate the peroxisomal matrix as a monomer.
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
authors.forename: Vladimir I
authors.initials: VI
authors.lastname: Titorenko
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Nicaud
authors.forename: Huijie
authors.initials: H
authors.lastname: Wang
authors.forename: Honey
authors.initials: H
authors.lastname: Chan
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rachubinski
mesh_terms: D000214:Acyl Coenzyme A / Q000187:drug effects / Q000378:metabolism*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D019791:Guanidine / Q000494:pharmacology; D009154:Mutation / Q000502:physiology; D010277:Parasympathomimetics / Q000494:pharmacology; D000074435:Peroxisome-Targeting Signal 1 Receptor; D020675:Peroxisomes / Q000187:drug effects / Q000201:enzymology*; D011108:Polymers / Q000378:metabolism*; D017510:Protein Folding; D020033:Protein Isoforms / Q000187:drug effects / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency / Q000235:genetics; D025062:Yarrowia / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*
chemical_list: D000214:Acyl Coenzyme A; D010277:Parasympathomimetics; D000074435:Peroxisome-Targeting Signal 1 Receptor; D011108:Polymers; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D005182:Flavin-Adenine Dinucleotide; D019791:Guanidine