Table 1.
The signaling pathways and molecules regulating ACSL4 expression.
| Cell or animal models | Signaling pathways or molecules | ACSL4 expression | Effect | References |
| MCF10-A, Hs578T, and SUM-159 | Integrin α6β4-mediated activation of Src and STAT3 | Downregulate | Protecting against changes of membrane lipid compositions and ferroptosis | [25] |
| HepG2; C57BL/6 J mice with a HFD | p115 binding to and mediating degradation of ACSL4 | Downregulate | UN | [26] |
| HUVEC cells | A20 interacting with ACSL4 directly | Downregulate | Protecting against ferroptosis | [27] |
| HepG2 and Huh7; primary hepatocytes | AA-mediated ubiquitin-proteasomal degradation of ACSL4 | Downregulate | UN | [28] |
| Caco-2 with hypoxia/reoxygenation; C57BL/6 mice with I/R | Sp1 binding to the promoter region of ACSL4 | Upregulate | Promoting ferroptosis | [29,30] |
| Human epithelial tumor cells and mesothelioma cells | Activation of Merlin/Hippo/YAP/TEAD4 pathway | Upregulate | Promoting ferroptosis | [31] |
| HepG2 and AML12; primary hepatocytes; Syrian hamsters | Activation of PPARδ | Upregulate | UN | [32] |
| H9c2 under hypoxia | SENP1-mediated deSUMOylation of ACSL4 | – | Protecting against ferroptosis | [33] |
| MA-10 | cAMP-dependent pathway-mediated activation of SHP2 | Upregulate | Increasing the production of steroid | [34] |
| CRL-1619, CRL-3367, CRL-6475, and CRL-1642 | IFN-γ-mediated activation of JAK/STAT1/IRF1 | Upregulate | Increasing the esterification of AA into PLs; promoting ferroptosis | [111] |
AA: Arachidonic acid; ACSL4: Acyl-CoA synthase 4; AML12: Mouse liver cells; cAMP: Cyclic adenosine monophosphate; Caco-2: Colon carcinoma cells; CRL-1619, CRL-3367, and CRL-6475: Human and mouse melanoma cells; CRL-1642: Lewis lung cancer cells; H9c2: Rat cardiac myocytes; HepG2 and Huh7: Hepatoma cells; HFD: High-fat diet; Hs578T and SUM-159: Breast carcinoma cells; HUVEC: Human umbilical vein endothelial cells; IFN: Interferon; I/R: Ischemia/reperfusion; IRF1: Interferon regulatory factor 1; JAK: Janus kinase; MA-10: Leydig cells; MCF10-A: Breast epithelial cells; PLs: Phospholipids; PPARδ: Peroxisome proliferator-activated receptor delta; SENP1: Sentrin-specific protease 1; SHP2: Src homology-2 domain-containing protein tyrosine phosphatase-2; Sp1: Specificity protein 1; STAT: Signal transducer and activator of transcription; TEAD4: Transcriptional enhanced associate domain; UN: Unknown; YAP: Yes-associated protein; –: Not available.