Acyl-CoA synthetase long-chain family member 3 (ACSL3)

Acyl-CoA synthetase long-chain family member 3 (ACSL3) is an enzyme that plays a central role in lipid metabolism by catalyzing the conversion of long-chain fatty acids into active fatty acyl-CoA esters [UniProt: P33121]. This activation is a mandatory first step for fatty acids to enter either degradative pathways like beta-oxidation or biosynthetic pathways for phospholipids and triacylglycerols [PubMed: 22442436]. ACSL3 is predominantly localized to the endoplasmic reticulum and the surface of lipid droplets, where it regulates the partitioning of fatty acids toward storage or utilization [NCBI Gene: 2181]. In oncology, ACSL3 is frequently upregulated, particularly in lung and prostate cancers, where it supports rapid tumor growth and survival by facilitating lipid reprogramming and protecting cells from ferroptosis [PubMed: 28416752, PubMed: 31604540]. It also serves as a host factor for several viruses, including Hepatitis C and poliovirus, which utilize ACSL3-mediated lipid remodeling for their replication cycles [PubMed: 21907144]. While pharmacological inhibition using tools like Triacsin C has shown promise in research models, therapeutic development focuses on achieving isoform specificity to minimize systemic metabolic side effects [PubMed: 24349272].

Other names

Long-chain fatty acid-CoA ligase 3Lignoceroyl-CoA synthaseACS3FACL3Fatty-acid-CoA ligase, long-chain 3

Inhibition of the enzymatic conversion of long-chain fatty acids to fatty acyl-CoA esters, thereby disrupting lipid synthesis, storage, and beta-oxidation pathways.