Transport of Activated Fatty Acids by the Peroxisomal ATP‐binding‐cassette Transporter Pxa2 in a Semi‐Intact Yeast Cell System
Open accessAbstract
In the yeast Saccharomyces cerevisiae, fatty acid β‐oxidation is restricted to peroxisomes. Previous studies have shown two possible routes by which fatty acids enter the peroxisome. The first route involves transport of medium‐chain fatty acids across the peroxisomal membrane as free fatty acids, followed by activation within the peroxisome by Faa2p, an acyl‐CoA synthetase. The second route involves transport of long‐chain fatty acids. Long‐chain fatty acids enter the peroxisome via a route that involves activation in the extraperoxisomal space, followed by transport across the peroxisomal membrane. It has been suggested that this transport is dependent upon the peroxisomal ATP‐binding‐cassette transporters Pxa1p and Pxa2p. In this paper we investigated whether Pxa2p is directly responsible for the transport of C18:1‐CoA, a long‐chain acyl‐CoA ester. Using protoplasts in which the plasma membrane has been selectively permeabilised by digitonin, we show that C18:1‐CoA, but not C8:0‐CoA, enters the peroxisome via Pxa2p, in an ATP‐dependent fashion. The results obtained may contribute to the elucidation of the primary defect in the human disease X‐linked adrenoleukodystrophy.
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The yeast Pxa1p/Pxa2p transporter is involved in the transport of long-chain fatty acyl-CoA esters from the cytoplasm, across the peroxisomal membrane, and into the interior of the peroxisome.
“This transporter somehow is involved in the transport of long-chain fatty acyl-CoA esters from the cytoplasm, across the peroxisomal membrane and into the interior of the peroxisome [Verleur et al., 1997;Hettema and Tabak, 2000].”
From ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: Role in diagnosis and clinical correlations (2001) · cites this paper as Verleur et al., 1997
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Kemp, S., Pujol, A., Waterham, H. R., van Geel, B. M., Boehm, C. D., Raymond, G. V., Cutting, G. R., Wanders, R. J. A., & Moser, H. W. (2001) · Human Mutation · doi:10.1002/humu.1227 · Cited by 332 · see citing works
Self-citationX-linked adrenoleukodystrophy: Clinical, metabolic, genetic and pathophysiological aspects
Kemp, S., Berger, J., & Aubourg, P. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.03.012 · Cited by 283 · see citing works
Peroxisomal ABC transporters: Structure, function and role in disease
Morita, M., & Imanaka, T. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.02.009 · Cited by 183 · see citing works
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Self-citationA key role for the peroxisomal<i>ABCD2</i>transporter in fatty acid homeostasis
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Self-citationPeroxisomal ABC Transporters: An Update
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Peroxisomes, myelination, and axonal integrity in the CNS
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- Authors
- Verleur, N., Hettema, E. H., Van Roermund, C. W. T., Tabak, H. F., & Wanders, R. J. A.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Wanders, Ronald J. A.
- Venue
- European Journal of Biochemistry
- Publisher
- Wiley
- Published
- 1997-11
- Volume
- 249
- Issue
- 3
- Pages
- 657-661
- ISSN
- 0014-2956 (ISSN-L)
- 1432-1033
- OpenAlex
- W2122276553
- Cited by
- 117
- References
- 2
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 3 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 1 · 2013: 4 · 2012: 8
- FWCI
- 4.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- fatty acid uptake, long-chain fatty acids, peroxisomes, fatty acid beta-oxidation, Saccharomyces cerevisiae, protoplasts, X-linked adrenoleukodystrophy
- MeSH terms
- Acyl Coenzyme A, Adenosine Triphosphate, Adrenoleukodystrophy, Biological Transport, Cell Membrane Permeability, Digitonin, Fatty Acids, Fungal Proteins, Humans, Microbodies, Oxidation-Reduction, Protoplasts, Saccharomyces cerevisiae, ATP-Binding Cassette Transporters, Saccharomyces cerevisiae Proteins
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