Adrenoleukodystrophy protein enhances association of very long-chain acyl-coenzyme a synthetase with the peroxisome

Takeshi Yamada, T. Taniwaki, N. Shinnoh, A. Uchiyama, N. Shimozawa, Y. Ohyagi, H. Asahara, J. Kira

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Abstract

Objective: To clarify the function of adrenoleukodystrophy protein (ALDP) using our ALDP-deficient mice established by gene targeting: Background: X-linked adrenoleukodystrophy (ALD) is characterized biochemically by the accumulation of very long-chain fatty acids (VLCFA) in tissues and body fluids, and is caused by impairment of peroxisomal β- oxidation. In ALD, very long-chain acyl-coenzyme A synthetase (VLACS), which is necessary for peroxisoreal β-oxidation, does not function. Methods: The ALDP-deficient mice and C57BL/6J mice were used. VLACS or ALDP were transiently expressed by lipofection in murine fibroblasts, and VLCFA β- oxidation was assayed. Liver peroxisomes were purified by sequential centrifugations and a Nycodenz gradient centrifugation. The peroxisomal localization of VLACS was compared between the mutant and control mice using a Western blot analysis. Results: Impairment of VLCFA β-oxidation in ALDP- deficient fibroblasts was not corrected by the additional expression of VLACS alone but was by the coexpression of VLACS and ALDP. Although the tissue- specific expression of VLACS was similar in ALDP-deficient and normal mice, peroxisomal VLACS was clearly lower in ALDP-deficient than in normal mice. Conclusions: ALDP plays a role in the peroxisomal localization of VLACS, and VLACS does not function unless localized in the peroxisome.

Original languageEnglish
Pages (from-to)614-616
Number of pages3
JournalNeurology
Volume52
Issue number3
Publication statusPublished - Feb 1 1999

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All Science Journal Classification (ASJC) codes

  • Clinical Neurology

Cite this

Yamada, T., Taniwaki, T., Shinnoh, N., Uchiyama, A., Shimozawa, N., Ohyagi, Y., ... Kira, J. (1999). Adrenoleukodystrophy protein enhances association of very long-chain acyl-coenzyme a synthetase with the peroxisome. Neurology, 52(3), 614-616.