Abstract
ATP-binding cassette (ABC) transporters constitute one of the largest superfamilies of conserved proteins from bacteria to mammals. In humans, three members of this family are expressed in the peroxisomal membrane and belong to the subfamily D: ABCD1 (ALDP), ABCD2 (ALDRP), and ABCD3 (PMP70). These half-transporters must dimerize to form a functional transporter, but they are thought to exist primarily as tetramers. They possess overlapping but specific substrate specificity, allowing the transport of various lipids into the peroxisomal matrix. The defects of ABCD1 and ABCD3 are responsible for two genetic disorders called X-linked adrenoleukodystrophy and congenital bile acid synthesis defect 5, respectively. In addition to their role in peroxisome metabolism, it has recently been proposed that peroxisomal ABC transporters participate in cell signaling and cell control, particularly in cancer. This review presents an overview of the knowledge on the structure, function, and mechanisms involving these proteins and their link to pathologies. We summarize the different in vitro and in vivo models existing across the species to study peroxisomal ABC transporters and the consequences of their defects. Finally, an overview of the known and possible interactome involving these proteins, which reveal putative and unexpected new functions, is shown and discussed.
Highlights
ATP-binding cassette (ABC) transporters constitute a superfamily of membrane transporter proteins that actively translocate a wide range of molecules, from simple molecules (fatty acids (FAs), sugars, nucleosides, and amino acids) to complex organic compounds [1]
Several studies have demonstrated that ABCD4 resides in the endoplasmic reticulum and lysosomes, and that its function is associated with cobalamin metabolism [3,5,6]
Transcriptomic, proteomic, and lipidomic studies, which have multiplied in the last few years, have confirmed and/or revealed the involvement of peroxisomal metabolism in various biological processes essential for cellular adaptation, brain homeostasis, or even immune response and inflammation
Summary
ATP-binding cassette (ABC) transporters constitute a superfamily of membrane transporter proteins that actively translocate a wide range of molecules, from simple molecules (fatty acids (FAs), sugars, nucleosides, and amino acids) to complex organic compounds (lipids, oligonucleotides, polysaccharides, and proteins) [1]. ABC transporters are distributed in the plasma membrane of both prokaryotes and eukaryotes, and in the membranes of the organelles of eukaryotic cells such as peroxisomes, mitochondria, lysosomes, and endoplasmic reticulum (ER). Based on their amino acid homology and structural configuration, ABC transporters in humans are classified into seven subfamilies, A to G, comprising a total of 48 ABC transporters, many of which are implicated in diseases [2]. Β-oxidation of FAs is a conserved process of peroxisomes by which acyl are degraded two carbons at a time beingbeing activated to form the corresponding. Peroxisomal β-oxidation may not be considered a simple catabolic process of fatty acids.
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