A Saccharomyces cerevisiae homolog of the human adrenoleukodystrophy transporter is a heterodimer of two half ATP-binding cassette transporters.

Shani, Noam; Valle, David

doi:10.1073/pnas.93.21.11901

Cited by 137 publications

(86 citation statements)

References 39 publications

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“…More than 100 putative ABC transporters have been identified in Arabidopsis (Davies and Coleman, 2000;Sánchez-Fernández et al, 2001). As shown in Figure 6, the Arabidopsis PXA1 protein resembles two yeast peroxisomal ABC transporters (Pxa1p/Pat2p/Pal1p and Pxa2p/Pat1p; Shani et al, 1995;Hettema et al, 1996;Shani and Valle, 1996;Swartzman et al, 1996) and four human transporters (PMP70/PXMP1, P70R, ALDP, and ALDRP; Gärtner et al, 1992Gärtner et al, , 1998Kamijo et al, 1992;Mosser et al, 1993;Lombard-Platet et al, 1996;Holzinger et al, 1999). Several of these proteins have been localized to the peroxisomal membrane (Kamijo et al, 1992;Contreras et al, 1994;Imanaka et al, 1996Imanaka et al, , 1999Swartzman et al, 1996;Holland and Blight, 1999), and experiments using semi-intact yeast cell systems show that oleic acid enters the peroxisome as a CoA ester using PXA2 in an ATPdependent manner (Verleur et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…The EAA-like domain (Figs. 5B, ovals, and 6) is a second conserved region on the cytoplasmic face of the protein between TM domains 4 and 5 and is thought to control substrate specificity by binding fatty acids (Shani et al, 1995;Shani and Valle, 1996). The mechanism of fatty acid transport by these peroxisomal proteins has not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…Yeast PXA1 and PXA2 deletion mutants have morphologically intact peroxisomes but have reduced (approximately 20%-50%) LCFA ␤-oxidation and consequently cannot use oleic acid as a carbon source (Shani et al, 1995;Hettema et al, 1996;Shani and Valle, 1996). The ␤-oxidation of short-chain fatty acids is unaffected, indicating that ␤-oxidation enzymes and matrix protein import remain intact (Hettema et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…The ␤-oxidation of short-chain fatty acids is unaffected, indicating that ␤-oxidation enzymes and matrix protein import remain intact (Hettema et al, 1996). The phenotype of the yeast pxa1/ pxa2 double mutant is comparable with the single mutants and Pxa1p and Pxa2p interact in yeast twohybrid assays and co-immunoprecipitation experiments, suggesting that the two proteins function together (Shani et al, 1995;Hettema et al, 1996;Shani and Valle, 1996). with the MegAlign program (DNASTAR, Inc., Madison, WI) using the ClustalW method.…”

Section: Discussionmentioning

confidence: 99%

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The Arabidopsis pxa1 Mutant Is Defective in an ATP-Binding Cassette Transporter-Like Protein Required for Peroxisomal Fatty Acid β-Oxidation

2001

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Peroxisomes are important organelles in plant metabolism, containing all the enzymes required for fatty acid ␤-oxidation. More than 20 proteins are required for peroxisomal biogenesis and maintenance. The Arabidopsis pxa1 mutant, originally isolated because it is resistant to the auxin indole-3-butyric acid (IBA), developmentally arrests when germinated without supplemental sucrose, suggesting defects in fatty acid ␤-oxidation. Because IBA is converted to the more abundant auxin, indole-3-acetic acid (IAA), in a mechanism that parallels ␤-oxidation, the mutant is likely to be IBA resistant because it cannot convert IBA to IAA. Adult pxa1 plants grow slowly compared with wild type, with smaller rosettes, fewer leaves, and shorter inflorescence stems, indicating that PXA1 is important throughout development. We identified the molecular defect in pxa1 using a map-based positional approach. PXA1 encodes a predicted peroxisomal ATP-binding cassette transporter that is 42% identical to the human adrenoleukodystrophy (ALD) protein, which is defective in patients with the demyelinating disorder X-linked ALD. Homology to ALD protein and other human and yeast peroxisomal transporters suggests that PXA1 imports coenzyme A esters of fatty acids and IBA into the peroxisome for ␤-oxidation. The pxa1 mutant makes fewer lateral roots than wild type, both in response to IBA and without exogenous hormones, suggesting that the IAA derived from IBA during seedling development promotes lateral root formation.Peroxisomes are small, ubiquitous organelles encased in a single lipid bilayer that contain hydrogen peroxide-producing oxidases and catalases to inactivate reactive molecules (for review, see Gerhardt, 1992; Kindl, 1993; Olsen, 1998; Tabak et al., 1999). Arabidopsis and other oilseed plants ␤-oxidize longchain fatty acids (LCFAs) in peroxisomes to provide energy during germination. Plant peroxisomes also contain enzymes that act in photorespiration (Olsen, 1998) and the catabolism of branched-chain amino acids (Gerhardt, 1992; Zolman et al., 2001). In addition, seedlings and senescing tissues contain specialized peroxisomes called glyoxysomes that convert acetyl-coenzyme A (CoA) to succinate, which is transported to the mitochondria where it fuels the tricarboxylic acid cycle (Gerhardt, 1992; Olsen, 1998).Mammals metabolize fatty acids in both mitochondria and peroxisomes, and each organelle shortens a distinct subset of fatty acids (Lazarow, 1993; Tabak et al., 1999). In contrast, plants and yeast catabolize fatty acids exclusively in peroxisomes (Gerhardt, 1992; Kindl, 1993). Because peroxisomes lack DNA, proteins required for ␤-oxidation and other peroxisomal processes are translated in the cytoplasm and then imported (Olsen, 1998;Subramani, 1998; Tabak et al., 1999). Peroxisomal matrix proteins contain one of two peroxisomal targeting signals (PTSs). The PTS1 is made up of the amino acids "SKL" (or a conserved variant) at the extreme C termini of peroxisomal matrix-bound proteins (Gould et al., 1989). The PEX5 recept...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The Arabidopsis pxa1 Mutant Is Defective in an ATP-Binding Cassette Transporter-Like Protein Required for Peroxisomal Fatty Acid β-Oxidation

2001

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“…Oxidation of the VLCFA C26:0 and C24:0 is impaired in X-ALD fibroblasts, suggesting that ABCD1 is involved in the import of VLCFAs into the peroxisome for degradation (45). Thus the observed ␤-oxidation defect must be secondary to the impaired transport of the substrate across the peroxisomal membrane in the absence of a functional transporter in these cells (20,58,64). In analogy with the work in yeast, it has been postulated that ABCD1 transports the CoA esters of VLCFAs across the peroxisomal membrane in mammals (63).…”

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confidence: 99%

A key role for the peroxisomalABCD2transporter in fatty acid homeostasis

Fourcade¹,

Ruíz²,

Camps³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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Identification of peroxisomal membrane proteins ofSaccharomyces cerevisiae by mass spectrometry

et al. 2001

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The identification of peroxisomal membrane proteins is very important to understand the import mechanisms of substrates and proteins into these organelles and the pathogenesis of human peroxisomal disorders like the Zellweger Syndrom. Peroxisomal membrane proteins were identified after separation by gel electrophoresis, tryptic digestion and mass spectrometric analysis. Using matrix assisted laser desorption/ionization-mass spectrometry (MALDI-MS) and nanoliquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS), it was possible to identify 45 proteins of isolated yeast peroxisomal membranes.

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A Saccharomyces cerevisiae homolog of the human adrenoleukodystrophy transporter is a heterodimer of two half ATP-binding cassette transporters.

Abstract: The adrenoleukodystrophy protein (ALDP) and the 70-kDa peroxisomal membrane protein (PMP70) This result predicts the presence of similar heterodimeric ABC transporters in the mammalian peroxisome membrane.

Cited by 137 publications

References 39 publications

The Arabidopsis pxa1 Mutant Is Defective in an ATP-Binding Cassette Transporter-Like Protein Required for Peroxisomal Fatty Acid β-Oxidation

The Arabidopsis pxa1 Mutant Is Defective in an ATP-Binding Cassette Transporter-Like Protein Required for Peroxisomal Fatty Acid β-Oxidation

A key role for the peroxisomalABCD2transporter in fatty acid homeostasis

Identification of peroxisomal membrane proteins ofSaccharomyces cerevisiae by mass spectrometry

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