title: Identification of a new fatty acid synthesis-transport machinery at the peroxisomal membrane.
abstract: The neurodegenerative disease X-linked adrenoleukodystrophy (X-ALD) is characterized by the abnormal accumulation of very long chain fatty acids. Mutations in the gene encoding the peroxisomal ATP-binding cassette half-transporter, adrenoleukodystrophy protein (ALDP), are the primary cause of X-ALD. To gain a better understanding of ALDP dysfunction, we searched for interaction partners of ALDP and identified binary interactions to proteins with functions in fatty acid synthesis (ACLY, FASN, and ACC) and activation (FATP4), constituting a thus far unknown fatty acid synthesis-transport machinery at the cytoplasmic side of the peroxisomal membrane. This machinery adds to the knowledge of the complex mechanisms of peroxisomal fatty acid metabolism at a molecular level and elucidates potential epigenetic mechanisms as regulatory processes in the pathogenesis and thus the clinical course of X-ALD.
authors: Department of Pediatrics and Pediatric Neurology, Faculty of Medicine, Georg August University, 37075 Göttingen, Germany.
authors: Merle
authors: M
authors: Hillebrand
authors: Department of Molecular Pediatrics, Dr. von Hauner Children's Hospital, Ludwig Maximilians University, 80337 Munich, Germany.
authors: Søren W
authors: SW
authors: Gersting
authors: Department of Molecular Pediatrics, Dr. von Hauner Children's Hospital, Ludwig Maximilians University, 80337 Munich, Germany.
authors: Amelie S
authors: AS
authors: Lotz-Havla
authors: Department of Dermatology, Venereology, and Allergology, Faculty of Medicine Georg August University, 37075 Göttingen, Germany.
authors: Annika
authors: A
authors: Schäfer
authors: Department of Pediatrics and Pediatric Neurology, Faculty of Medicine, Georg August University, 37075 Göttingen, Germany.
authors: Hendrik
authors: H
authors: Rosewich
authors: Institute of Microbiology and Genetics, Department of Molecular Microbiology and Genetics, Georg August University, 37077 Göttingen, Germany.
authors: Oliver
authors: O
authors: Valerius
authors: Department of Molecular Pediatrics, Dr. von Hauner Children's Hospital, Ludwig Maximilians University, 80337 Munich, Germany.
authors: Ania C
authors: AC
authors: Muntau
authors: Department of Pediatrics and Pediatric Neurology, Faculty of Medicine, Georg August University, 37075 Göttingen, Germany. Electronic address: gaertnj@med.uni-goettingen.de.
authors: Jutta
authors: J
authors: Gärtner
mesh_terms: D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000326:Adrenoleukodystrophy / Q000378:metabolism; D001692:Biological Transport; D064429:Fatty Acid Synthases / Q000378:metabolism; D050612:Fatty Acid Transport Proteins / Q000378:metabolism*; D005227:Fatty Acids / Q000096:biosynthesis* / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D007425:Intracellular Membranes / Q000378:metabolism*; D020675:Peroxisomes / Q000378:metabolism*; D013057:Spectrum Analysis
chemical_list: C115572:ABCD1 protein, human; C063305:ABCD3 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D064429:Fatty Acid Synthases; D000103:Acetyl-CoA Carboxylase