The gene responsible for adrenoleukodystrophy encodes a peroxisomal membrane protein
Abstract
Adrenoleukodystrophy is a severe genetic demyelinating disease associated with an impairment of beta-oxidation of very long chain fatty acids (VLCFA) in peroxisomes. Earlier studies had suggested that a deficiency in VLCFA CoA synthetase was the primary defect. A candidate adrenoleukodystrophy gene has recently been cloned and was found unexpectedly to encode a putative ATP-binding cassette transporter. We have raised monoclonal antibodies against this protein, that detect a 75kDa band. This protein was absent in several patients with adrenoleukodystrophy. Immunofluorescence and immunoelectron microscopy showed that the adrenoleukodystrophy protein (ALDP) is associated with the peroxisomal membrane. Distinct immunofluorescence patterns were observed in cell lines from patients with Zellweger syndrome (a peroxisomal biogenesis disorder) belonging to different complementation groups.
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The ABCD1 gene encodes the ABCD1/ALD protein of 745 amino acids, an ATP-binding cassette transmembrane half-transporter required for the import of coenzyme A-activated very-long-chain fatty acids (VLCFAs; >C22:0) into peroxisomes for degradation.
“It encodes the ABCD1/ALD protein of 745 amino acids, an ATP-binding cassette transmembrane half-transporter required for the import of coenzyme A-activated very-long-chain fatty acids (VLCFAs; >C22:0) into peroxisomes for degradation [3,4].”
From Structure and Function of the ABCD1 Variant Database: 20 Years, 940 Pathogenic Variants, and 3400 Cases of Adrenoleukodystrophy (2022) · cites this paper as [3]
ALDP is a 745-amino-acid-long ATP-binding cassette (ABC) transporter.
“ALDP is a 745-amino-acid-long ATP-binding cassette (ABC) transporter [137].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [137]
The nucleotide binding fold of ALDP is located toward the cytoplasmic surface of the peroxisomal membrane.
“The nucleotide binding fold of ALDP is located toward the cytoplasmic surface of the peroxisomal membrane [Mosser et al., 1994;Watkins et al., 1995].”
From ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: Role in diagnosis and clinical correlations (2001) · cites this paper as Mosser et al., 1994
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- Authors
- Mosser, J., Lutz, Y., Stoeckel, M. E., Sarde, C. O., Kretz, C., Douar, A. M., Lopez, J., Aubourg, P., & Mandel, J. L.
- Affiliations
- Inserm (FR)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Mandel, Jean Louis
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 1994
- Volume
- 3
- Issue
- 2
- Pages
- 265-271
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2167246280
- Cited by
- 281
- References
- 0
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 12 · 2023: 5 · 2022: 8 · 2021: 16 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 4 · 2015: 6 · 2014: 6 · 2013: 6 · 2012: 6
- FWCI
- 13.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- adrenoleukodystrophy, peroxisomal membrane proteins, very long chain fatty acid beta-oxidation, peroxisomes, ABC transporters, Zellweger syndrome, peroxisome biogenesis disorders, complementation groups, demyelinating disease, gene cloning
- MeSH terms
- ATP Binding Cassette Transporter, Subfamily D, Member 1, Adrenoleukodystrophy, Animals, Antibodies, Monoclonal, Base Sequence, Carrier Proteins, Cells, Cultured, Chlorocebus aethiops, Fibroblasts, Genes, Carcinoma, Hepatocellular, Humans, Intracellular Membranes, Liver Neoplasms, Male, Membrane Proteins, Microbodies, Molecular Sequence Data, Recombinant Fusion Proteins, Transfection, Tumor Cells, Cultured, Zellweger Syndrome, Microscopy, Immunoelectron, ATP-Binding Cassette Transporters
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