ACSL4
ACSL4 (acyl-CoA synthetase long chain family member 4, also known as ACS4, LACS4 and FACL4) is a long-chain fatty-acid-CoA ligase that converts free fatty acids into acyl-CoA esters. It preferentially uses arachidonate and acts as an activator of ferroptosis. Browse Assay Genie's current range of ACSL4 research reagents below, or read on for the biology behind the target.
ACSL4 catalyses the conversion of long-chain fatty acids to their active form, acyl-CoA. These products feed both the synthesis of cellular lipids and degradation by beta-oxidation. The enzyme preferentially activates arachidonate and eicosapentaenoate, and among the epoxyeicosatrienoic acids (EETs) it favours 8,9-EET, followed by 14,15-EET, 5,6-EET and 11,12-EET. Through its control of unesterified EET levels it modulates glucose-stimulated insulin secretion, and it also modulates prostaglandin E2 secretion.
ACSL4 is an activator of ferroptosis. By activating polyunsaturated fatty acids, especially arachidonate and adrenate, it generates the primary lipid-peroxidation substrates that contribute to this form of cell death. This makes the ACSL4 protein a frequent subject in studies of lipid peroxidation and ferroptosis.
The ACSL4 gene encodes an isozyme of the long-chain fatty-acid-coenzyme A ligase family, which belongs to the ATP-dependent AMP-binding enzyme family. Isozymes differ in substrate specificity, subcellular localisation and tissue distribution, but all convert free long-chain fatty acids into fatty acyl-CoA esters. ACSL4 is found at the mitochondrial outer membrane, the endoplasmic reticulum membrane and the cell membrane, and alternative splicing generates multiple transcript variants. The gene has also been listed as MRX63 and MRX68 (mental retardation, X-linked 63 and 68), and the absence of the enzyme may contribute to cognitive disability or Alport syndrome. Mouse and rat orthologs are both named Acsl4.
ACSL4 activates arachidonate and adrenate, generating the primary lipid-peroxidation substrates that contribute to ferroptosis.
The enzyme converts long-chain fatty acids to acyl-CoA for lipid synthesis and beta-oxidation, with a preference for arachidonate.
ACSL4 modulates glucose-stimulated insulin secretion by regulating the levels of unesterified EETs.
ACSL4 modulates prostaglandin E2 secretion and shows defined preferences among EET substrates.
ACSL4 catalyses the conversion of long-chain fatty acids to acyl-CoA, supporting lipid synthesis and beta-oxidation. It preferentially activates arachidonate and eicosapentaenoate, modulates insulin and prostaglandin E2 secretion, and activates ferroptosis by providing polyunsaturated fatty acid substrates for lipid peroxidation.
ACSL4 is also called ACS4, LACS4 and FACL4. Earlier names include fatty-acid-Coenzyme A ligase, long-chain 4, and the X-linked mental retardation designations MRX63 and MRX68. UniProt names the protein long-chain-fatty-acid--CoA ligase 4, and alternative splicing yields multiple transcript variants.
NCBI Gene reports that absence of this enzyme may contribute to cognitive disability or Alport syndrome. Orthologs exist in mouse and rat, both named Acsl4. Check the datasheet of any product for its validated reactivity.
Other long-chain acyl-CoA synthetase family members involved in fatty acid activation and lipid metabolism.
Gene and protein annotations from HGNC, NCBI Gene and UniProt O60488; product specifications from Assay Genie datasheets.