Peroxisomal acyl-CoA synthetases

Peroxisomes carry out many essential lipid metabolic functions. Nearly all of these functions require that an acyl group—either a fatty acid or the acyl side chain of a steroid derivative—be thioesterified to coenzyme A (CoA) for subsequent reactions to proceed. This thioesterification, or “activation”, reaction, catalyzed by enzymes belonging to the acyl-CoA synthetase family, is thus central to cellular lipid metabolism. However, despite our rather thorough understanding of peroxisomal metabolic pathways, surprisingly little is known about the specific peroxisomal acyl-CoA synthetases that participate in these pathways. Of the 26 acyl-CoA synthetases encoded by the human and mouse genomes, only a few have been reported to be peroxisomal, including ACSL4, SLC27A2, and SLC27A4. In this review, we briefly describe the primary peroxisomal lipid metabolic pathways in which fatty acyl-CoAs participate. Then, we examine the evidence for presence and functions of acyl-CoA synthetases in peroxisomes, much of which was obtained before the existence of multiple acyl-CoA synthetase isoenzymes was known. Finally, we discuss the role(s) of peroxisome-specific acyl-CoA synthetase isoforms in lipid metabolism. This article is part of a Special Issue entitled: Metabolic Functions and Biogenesis of Peroxisomes in Health and Disease.

► Peroxisomes carry out several metabolic processes requiring activated fatty acids (acyl-CoAs).
► Acyl-CoA synthetases catalyze the formation of activated fatty acids.
► Peroxisomes have acyl-CoA synthetase activity, but only three of the 26 mammalian enzymes have been detected in peroxisomes.
► This article summarizes the current state of knowledge of peroxisomal acyl-CoA synthetase function.