title: Peroxisomal ABC transporters: functions and mechanism.
abstract: Peroxisomes are arguably the most biochemically versatile of all eukaryotic organelles. Their metabolic functions vary between different organisms, between different tissue types of the same organism and even between different developmental stages or in response to changed environmental conditions. New functions for peroxisomes are still being discovered and their importance is underscored by the severe phenotypes that can arise as a result of peroxisome dysfunction. The β-oxidation pathway is central to peroxisomal metabolism, but the substrates processed are very diverse, reflecting the diversity of peroxisomes across species. Substrates for β-oxidation enter peroxisomes via ATP-binding cassette (ABC) transporters of subfamily D; (ABCD) and are activated by specific acyl CoA synthetases for further metabolism. Humans have three peroxisomal ABCD family members, which are half transporters that homodimerize and have distinct but partially overlapping substrate specificity; Saccharomyces cerevisiae has two half transporters that heterodimerize and plants have a single peroxisomal ABC transporter that is a fused heterodimer and which appears to be the single entry point into peroxisomes for a very wide variety of β-oxidation substrates. Our studies suggest that the Arabidopsis peroxisomal ABC transporter AtABCD1 accepts acyl CoA substrates, cleaves them before or during transport followed by reactivation by peroxisomal synthetases. We propose that this is a general mechanism to provide specificity to this class of transporters and by which amphipathic compounds are moved across peroxisome membranes.
authors.affiliation: Centre for Plant Sciences, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, U.K. A.baker@leeds.ac.uk.
authors.forename: Alison
authors.initials: A
authors.lastname: Baker
authors.affiliation: Centre for Plant Sciences, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, U.K.
authors.forename: David J
authors.initials: DJ
authors.lastname: Carrier
authors.affiliation: Biological Chemistry and Crop Protection Department, Rothamsted Research, Harpenden, AL5 2JQ, U.K.
authors.forename: Theresia
authors.initials: T
authors.lastname: Schaedler
authors.affiliation: Laboratory of Genetic Metabolic Diseases, Departments of Pediatrics and Clinical Chemistry, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Hans R
authors.initials: HR
authors.lastname: Waterham
authors.affiliation: Laboratory of Genetic Metabolic Diseases, Departments of Pediatrics and Clinical Chemistry, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Carlo W
authors.initials: CW
authors.lastname: van Roermund
authors.forename: Frederica L
authors.initials: FL
authors.lastname: Theodoulou
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000378:metabolism*; D029681:Arabidopsis Proteins / Q000737:chemistry / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000378:metabolism*; D011487:Protein Conformation; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D029681:Arabidopsis Proteins; D005227:Fatty Acids; D029701:Saccharomyces cerevisiae Proteins; D003066:Coenzyme A Ligases
keywords: ATP-binding cassette (ABC) transporter; acyl-CoA; asymmetry; peroxisome; thioesterase; β-oxidation