Peroxisomal very long chain fatty acid β-oxidation activity is determined by the level of adrenodeukodystrophy protein (ALDP) expression

Research output: Contribution to journalArticle

Abstract

Impaired peroxisomal β-oxidation of saturated very long chain fatty acids (VLCFA, ≥C22:0) results in increased VLCFA levels in the tissues and body fluids of patients with disorders of peroxisomal biogenesis (i.e., Zellweger syndrome and neonatal adrenoleukodystrophy) and single peroxisomal protein defects (i.e., X-linked adrenoleukodystrophy (X-ALD) and acyl-CoA oxidase deficiency). We show that SV40T transformation also results in impaired peroxisomal β-oxidation and VLCFA accumulation despite the presence of abundant peroxisomes. To explore the mechanism responsible for this observation, we have examined expression of key components of peroxisomal VLCFA β-oxidation. We found that expression of both acyl-CoA oxidase, the rate limiting enzyme of peroxisomal VLCFA β-oxidation and the adrenoleukodystrophy protein (ALDP), the defective gene product in X-ALD, are reduced after SV40T transformation. Surprisingly, ALDP overexpression by itself restores peroxisomal VLCFA β-oxidation in SV40T-transformed control and X-ALD cells. These results demonstrate that ALDP is a fundamental component in VLCFA peroxisomal β-oxidation and may serve as a 'gatekeeper' for VLCFA homeostasis.

Original languageEnglish (US)
Pages (from-to)91-99
Number of pages9
JournalMolecular genetics and metabolism
Volume66
Issue number2
DOIs
StatePublished - Feb 1999

Keywords

  • ALDP
  • Peroxisome SV40T antigen transformation
  • X-linked adrenoleukodystrophy
  • β-oxidation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

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