title: Suppression of peroxisomal membrane protein defects by peroxisomal ATP binding cassette (ABC) proteins.
abstract: X-Linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder characterized by reduced peroxisomal very long chain fatty acid (VLCFA) beta-oxidation. The X - ALD gene product (ALDP) is a peroxisomal transmembrane protein with an ATP binding cassette (ABC). ALDP and three other ABC proteins (PMP70, ALDR, P70R) localize to the peroxisomal membrane. The function of this family of peroxisomal membrane proteins is unknown. We used complementation studies to begin analysis of their role in VLCFA beta-oxidation and on the peroxisomal membrane. Expression of either ALDP or PMP70 restores VLCFA beta-oxidation in X-ALD fibroblasts, indicating overlapping functions. Their expression also restores peroxisome biogenesis in cells that are deficient in the peroxisomal membrane protein Pex2p. Thus it is likely that complex protein interactions are involved in the function and biogenesis of peroxisomal membranes that may contribute to disease heterogeneity.
authors.affiliation: Kennedy Krieger Research Institute, 707 North Broadway, Baltimore, MD 21205, USA. lita@welchlink.welch.jhu.edu
authors.forename: L T
authors.initials: LT
authors.lastname: Braiterman
authors.forename: S
authors.initials: S
authors.lastname: Zheng
authors.forename: P A
authors.initials: PA
authors.lastname: Watkins
authors.forename: M T
authors.initials: MT
authors.lastname: Geraghty
authors.forename: G
authors.initials: G
authors.lastname: Johnson
authors.forename: M C
authors.initials: MC
authors.lastname: McGuinness
authors.forename: A B
authors.initials: AB
authors.lastname: Moser
authors.forename: K D
authors.initials: KD
authors.lastname: Smith
mesh_terms: D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology*; D000326:Adrenoleukodystrophy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D003360:Cosmids; D005227:Fatty Acids / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005816:Genetic Complementation Test; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D008830:Microbodies / Q000378:metabolism*; D010084:Oxidation-Reduction; D000074428:Peroxisomal Biogenesis Factor 2; D014960:X Chromosome / Q000235:genetics
chemical_list: C115572:ABCD1 protein, human; C063305:ABCD3 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; D005227:Fatty Acids; D008565:Membrane Proteins; D000074428:Peroxisomal Biogenesis Factor 2