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.

X10 expansion microscopy enables 25‐nm resolution on conventional microscopes

“…X10, whose resolution is at the size of the probes, suffers less from this problem. Assuming that the Pmp70 epitopes surpass the peroxisome membrane by ~5 nm 30 and that the protein and antibody orientations are randomized after the permeabilization of the 6.8‐nm‐thick peroxisome membrane, the displacement induced by the antibodies is ~6 nm (Fig EV3). …”

Peroxisomal ACBD4 interacts with VAPB and promotes ER-peroxisome associations

“…In these cases increased levels of very-long-chain fatty acids (VLCFAs) were detected in patient cells likely due to reduced import into peroxisomes. This suggested a role for ACBD5 in binding VLCFAs in the cytosol and facilitating their transport into peroxisomes which would then be mediated by the peroxisomal ABC transporters at the peroxisomal membrane 35 , 36 . It is not clear if ACBD5 interacts with the ABC transporters, with a recent study failing to identify ACBD5 as an interacting partner of ABCD2, 37 nor how the tethering function of ACBD5 is linked to its function in β-oxidation of VLCFAs.…”

Plant membrane-protein mediated intracellular traffic of fatty acids and acyl lipids

“…Finally, the substrate for ABCA9 -free FAs or acyl-CoA -has to be identified. Here somewhat more advanced studies on the peroxisomal FA-importer ABCD1 (see [58]) might serve as a blueprint.…”

“…Thus, it has long been supposed that transporters in the plastid envelope membranes could play an essential role in the uptake of pyruvate from the cytosol for FA synthesis, export and subsequent acyl lipid production. [16,55] [58] Once synthesized, acyl residues are either integrated into lipids via plastid-resident acyltransferases, or released as free FAs by hydrolysis via acyl-ACP thioesterases at the stroma-side of the plastid inner envelope (IE) [5,12]. Only very recently the action of the plastid intrinsic phospholipase PLIP1 was proposed to initiate a mechanism leading to plastid FA export [18 and the precise localization of LACS enzyme activity towards the ER lumen, cytosol or at plastid-ER contact sites, however, are still unclear.…”