The peroxisomal ABC transporter family

Abstract

This review describes the current state of knowledge about the ABCD family of peroxisomal half adenosine-triphosphate-binding cassette (ABC) transporters. ABCDs are predicted to be present in a variety of eukaryotic organisms, although at present, only ABCDs in the yeast Saccharomyces cerevisiae, the plant Arabidopsis thaliana, and different mammalian species have been identified and characterized to any significant extent. The functional role of none of these ABCDs has been established definitively and awaits successful reconstitution of ABCDs, either as homo-or heterodimers into liposomes, followed by transport studies. Data obtained in S. cerevisiae suggest that the two ABCDs, which have been identified in this organism, form a heterodimer, which actually transports acyl coenzyme A esters across the peroxisomal membrane. In mammals, four ABCDs have been identified, of which one [adrenoleukodystrophy protein (ALDP)] has been implicated in the transport of the coenzyme A esters of very-long-chain fatty acids. Mutations in the gene (ABCD1) encoding ALDP are the cause of a severe X-linked disease, called X-linked adrenoleukodystrophy. The availability of mutant mice in which Abcd1, Abcd2, or Abcd3 have been disrupted will help to resolve the true role of the peroxisomal half-ABC transporters.

The Arabidopsis Peroxisomal ABC Transporter, Comatose, Complements the Saccharomyces cerevisiae pxa1 pxa2Δ Mutant for Metabolism of Long-chain Fatty Acids and Exhibits Fatty Acyl-CoA-stimulated ATPase Activity

“…Evidence from yeast suggests that Pxa1/Pxa2p transports FA-CoAs and not FA (10), suggesting, by extension, that the same is also true for ALDP and CTS, because they complement the pxa1 pxa2⌬ mutant (Ref. 9 and this study) and the peroxisomal synthetase Faa2p is not required for metabolism of fatty acids with chain lengths longer than C14 (2). Both cytosolic and peroxisomal acyl-CoA synthetases exist in Arabidopsis (29,64,65) but genetic data imply that CTS might transport free acids and not CoAs.…”

“…Peroxisomes perform a range of different functions, including ␤-oxidation of fatty acids (FA) 2 and synthesis and degradation of bioactive, lipid-derived molecules. Import of substrates for peroxisomal metabolism is mediated by ATP binding cassette (ABC) transporters belonging to subclass D (1,2).…”

“…Import of substrates for peroxisomal metabolism is mediated by ATP binding cassette (ABC) transporters belonging to subclass D (1,2). ABC transporters are composed of a minimum of four functional domains: two transmembrane domains, involved in substrate binding and translocation, and two nucleotide binding domains (NBDs) that bind and hydrolyze ATP, providing energy for transport (3,4).…”

“…The human ABCD transporter subfamily comprises four half-size members: adrenoleukodystrophy protein (ALDP), ALD-related protein, the 70-kDa peroxisomal membrane protein (PMP70), and PMP70-related protein (PMP70R/PMP69) (1,2). Although ALDP, ALD-related protein, and PMP70 have been implicated in lipid transport across the peroxisomal membrane (2,(11)(12)(13), the precise biochemical functions of these transporters are not well understood.…”

“…Although ALDP, ALD-related protein, and PMP70 have been implicated in lipid transport across the peroxisomal membrane (2,(11)(12)(13), the precise biochemical functions of these transporters are not well understood. However, ALDP partially complements the yeast pxa1 pxa2⌬ mutant for growth on oleate and ␤-oxidation of long-chain FAs (9), suggesting that ALDP acts as a homodimeric transporter that accepts acyl-CoA esters (9).…”