Peroxisomal ABC transporters: functions and mechanism.

Alison Baker,Frederica L Theodoulou,David J Carrier,Hans R Waterham,Carlo W Van Roermund,Theresia Schaedler

doi:10.1042/bst20150127

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.

Highlights

Peroxisome functions and the requirement for transportPeroxisomes are single membrane-delimited organelles found in almost all eukaryotic cells
Peroxisomal β-oxidation is important for synthesis of some bioactive molecules such as docosahexaenoic acid in mammals [2] and the plant hormone jasmonic acid (JA) which is synthesized from its precursor 12-oxophytodienoic acid (OPDA) by three rounds of β-oxidation [6]
Non-esterified fatty acids can enter the peroxisome independently of the ATP-binding cassette (ABC) transporter and are activated by the peroxisomal acyl-CoA synthetase, Faa2p, prior to β-oxidation [14], a process which requires the activity of the peroxisomal ATP carrier, Ant1p [18,19]

Summary

Introduction

Peroxisome functions and the requirement for transportPeroxisomes are single membrane-delimited organelles found in almost all eukaryotic cells. Few peroxisomal transporters have been identified but it is well-established that peroxisome localized members of ATP-binding cassette (ABC) subfamily D mediate uptake of substrates for β-oxidation [10]. Non-esterified fatty acids can enter the peroxisome independently of the ABC transporter and are activated by the peroxisomal acyl-CoA synthetase, Faa2p (fatty acid activation protein 2), prior to β-oxidation [14], a process which requires the activity of the peroxisomal ATP carrier, Ant1p (adenine nucleotide transporter1) [18,19].

Results

Conclusion