Identification of a new fatty acid synthesis-transport machinery at the peroxisomal membrane

J Biol Chem. 2012 Jan 2;287(1):210-221. doi: 10.1074/jbc.M111.272732. Epub 2011 Nov 1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters / metabolism
  • Acetyl-CoA Carboxylase / metabolism
  • Adrenoleukodystrophy / metabolism
  • Biological Transport
  • Fatty Acid Synthases / metabolism
  • Fatty Acid Transport Proteins / metabolism*
  • Fatty Acids / biosynthesis*
  • Fatty Acids / metabolism*
  • Fluorescence Resonance Energy Transfer
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • Intracellular Membranes / metabolism*
  • Peroxisomes / metabolism*
  • Spectrum Analysis

Substances

  • ABCD1 protein, human
  • ABCD3 protein, human
  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters
  • Fatty Acid Transport Proteins
  • Fatty Acids
  • Fatty Acid Synthases
  • Acetyl-CoA Carboxylase