title: Assembly of alcohol oxidase in peroxisomes of the yeast Hansenula polymorpha requires the cofactor flavin adenine dinucleotide.
abstract: The peroxisomal flavoprotein alcohol oxidase (AO) is an octamer (600 kDa) consisting of eight identical subunits, each of which contains one flavin adenine dinucleotide molecule as a cofactor. Studies on a riboflavin (Rf) auxotrophic mutant of the yeast Hansenula polymorpha revealed that limitation of the cofactor led to drastic effects on AO import and assembly as well as peroxisome proliferation. Compared to wild-type control cells Rf-limitation led to 1) reduced levels of AO protein, 2) reduced levels of correctly assembled and activated AO inside peroxisomes, 3) a partial inhibition of peroxisomal protein import, leading to the accumulation of precursors of matrix proteins in the cytosol, and 4) a significant increase in peroxisome number. We argue that the inhibition of import may result from the saturation of a peroxisomal molecular chaperone under conditions that normal assembly of a major matrix protein inside the target organelle is prevented.
authors: Laboratory of Electron Microscopy, University of Groningen, Haren, The Netherlands.
authors: M E
authors: ME
authors: Evers
authors: V I
authors: VI
authors: Titorenko
authors: I J
authors: IJ
authors: van der Klei
authors: W
authors: W
authors: Harder
authors: M
authors: M
authors: Veenhuis
mesh_terms: D000429:Alcohol Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D001693:Biological Transport, Active; D004789:Enzyme Activation; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism*; D007150:Immunohistochemistry; D008830:Microbodies / Q000378:metabolism; D008854:Microscopy, Electron; D018832:Molecular Chaperones / Q000378:metabolism; D009154:Mutation; D010843:Pichia / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D011487:Protein Conformation; D012256:Riboflavin / Q000235:genetics
chemical_list: D018832:Molecular Chaperones; D005182:Flavin-Adenine Dinucleotide; D000429:Alcohol Oxidoreductases; C019643:alcohol oxidase; D012256:Riboflavin