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. 2023 Jul 5;136(21):2521–2537. doi: 10.1097/CM9.0000000000002533

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Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.

This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

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The role of ACSL4 in FA metabolism. (A) ACSL4 remodels the PL composition of the cellular membrane. (B) The suppression of ACSL4 reduced the esterification of AA into PLs and, thereby, increased the production of eicosanoids. (C) Intracellular free AAs translocate to the intramitochondrial compartment through the ACSL4/DBI/TSPO/ACOT2 pathway and then regulate steroidogenesis by enhancing StAR. Created with BioRender.com. AA: Arachidonic acid; AA-CoA: Arachidonoyl-coenzyme A (CoA); ACOT2: Acyl-CoA thioesterase; ACSL4: Acyl-CoA synthase 4; ACTH: Adrenocorticotropic hormone; cAMP: Cyclic adenosine monophosphate; CoX: Cyclooxygenase; CYP450: Cytochrome P450; DBI: Diazepam-binding inhibitor; EETs: Epoxyeicosatrienoic acids; ETE: Eicosatetraenoic acid; FA: Fatty acid; 5-HETEs: 5-Hydroxyeicosatetraenoic acids; 5-HPETE: 5-Hydroperoxyeicosatetraenoic acid; LOX: Lipoxygenase; LTs: Leukotrienes; LXs: Lipoxins; LH: Luteinizing hormone; PC: Phosphatidylcholine; PE: Phosphatidylethanolamine; PGs: Prostaglandins; PI: Phosphatidylinositol; PKA: Protein kinase A; PLs: Phospholipids; StAR: Steroidogenic acute regulatory protein; TSPO: Translocator protein; TXs: Thromboxanes; TZDs: Thiazolidinediones.