Affinage

ACSL1

Long-chain-fatty-acid--CoA ligase 1 · UniProt P33121

Length
698 aa
Mass
77.9 kDa
Annotated
2026-04-28
100 papers in source corpus 29 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ACSL1 is a long-chain acyl-CoA synthetase that activates fatty acids (C10–C18 saturated and unsaturated) to their CoA thioesters, channeling lipid substrates into β-oxidation, membrane lipid remodeling, and signaling pathways (PMID:8973631, PMID:33152322). ACSL1 localizes predominantly to the mitochondrial outer membrane via its N-terminal 100 amino acids through interaction with CPT1b, and this localization is dynamically regulated by TBK1 scaffolding (directing substrates toward β-oxidation) and sortilin-mediated endolysosomal trafficking for degradation (PMID:34511469, PMID:33152322, PMID:39232011). ACSL1 participates in ferroptosis by incorporating polyunsaturated fatty acids into triacylglycerols and by promoting N-myristoylation and membrane targeting of FSP1, and it mediates TNFα-driven inflammatory signaling through the NF-κB/JNK/ERK cascade in monocytes (PMID:33854057, PMID:36882396, PMID:30845379, PMID:37658104). Acsl1 knockout in mice causes lethal skin barrier defects due to failure of linoleic acid activation required for ω-O-acylceramide synthesis, and MCL-1 directly stabilizes ACSL1 through BH3-groove binding to sustain long-chain fatty acid oxidation in vivo (PMID:34813948, PMID:38503284).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1996 High

    Establishing that ACSL1 is a bona fide long-chain acyl-CoA synthetase with defined substrate specificity resolved the enzyme's catalytic identity and showed that all five structural regions are required for activity.

    Evidence Recombinant rat ACSL1 purified from E. coli, enzymatic activity assays and deletion mutagenesis

    PMID:8973631

    Open questions at the time
    • No crystal structure available
    • Catalytic mechanism at atomic level unresolved
    • Isoform-specific substrate channeling not tested
  2. 2000 High

    Demonstrating that ACSL1 catalyzes stereoselective thioesterification of NSAID 2-arylpropionic acids expanded the enzyme's known substrate repertoire beyond endogenous fatty acids to xenobiotic metabolism.

    Evidence Purified recombinant ACSL1 kinetic assays with ibuprofen/fenoprofen enantiomers in vitro

    PMID:10725307

    Open questions at the time
    • In vivo relevance for NSAID chiral inversion not confirmed
    • Structural basis for stereoselectivity unknown
  3. 2010 High

    Showing that ACSL1 is required for adiponectin/insulin-stimulated AMPK activation in adipocytes linked acyl-CoA synthetase activity to energy-sensing signaling, not just metabolic flux.

    Evidence siRNA knockdown in mouse adipocytes with AMP/ATP ratio, AMPK phosphorylation, and fatty acid uptake readouts

    PMID:20667975

    Open questions at the time
    • Whether ACSL1 directly generates AMP or acts indirectly via acyl-CoA consumption unresolved
    • Contribution relative to FATP1 not fully delineated
  4. 2011 High

    Resolving that ACSL1 localizes to mitochondria (not the plasma membrane) and drives fatty acid uptake via metabolic trapping clarified that ACSL1 promotes uptake indirectly rather than functioning as a transporter.

    Evidence Stable overexpression in 3T3-L1 adipocytes and hepatoma cells with confocal microscopy, subcellular fractionation, and uptake assays

    PMID:22022213 PMID:23024797

    Open questions at the time
    • Mechanism of metabolic trapping at molecular detail unclear
    • Whether ACSL1 also transiently localizes to other compartments not excluded
  5. 2016 High

    Identifying SREBP2-dependent transcriptional activation of ACSL1 via a sterol regulatory element in its C-promoter revealed how cholesterol homeostasis programs coordinate fatty acid activation.

    Evidence Promoter mutagenesis, EMSA, SREBP2 knockdown in HepG2, and in vivo statin/diet models in hamsters and mice

    PMID:26728456

    Open questions at the time
    • Functional significance of alternative ACSL1 promoter usage not fully characterized
    • SREBP1 vs SREBP2 selectivity mechanism unknown
  6. 2018 High

    Demonstrating that hepatic ACSL1 depletion causes hypercholesterolemia and that FXR represses ACSL1 placed ACSL1 within the bile acid–cholesterol regulatory network.

    Evidence Adenoviral shRNA knockdown in mouse liver, genome-wide expression profiling, FXR KO mice with agonist treatment

    PMID:30580099

    Open questions at the time
    • Whether ACSL1 regulation by FXR is direct or indirect not fully resolved
    • Downstream lipid species mediating cholesterol dysregulation not identified
  7. 2019 Medium

    Showing that ACSL1 is required for TNFα-induced NF-κB-dependent pro-inflammatory monocyte polarization established ACSL1 as a mediator of innate immune activation independent of β-oxidation.

    Evidence Triacsin C inhibition and siRNA knockdown in human monocytes with flow cytometry, ELISA, NF-κB reporter and phosphorylation assays

    PMID:30845379

    Open questions at the time
    • Specific acyl-CoA species or lipid mediators linking ACSL1 to NF-κB activation not identified
    • Triacsin C inhibits multiple ACSLs, limiting isoform specificity
  8. 2020 High

    Discovering that TBK1 acts as a kinase-independent scaffold to retain ACSL1 at mitochondria during fasting, with loss shifting ACSL1 to the ER, established a regulated mechanism for partitioning fatty acids between oxidation and re-esterification.

    Evidence Liver-specific TBK1 KO mice, kinase-dead rescue, co-IP, subcellular fractionation, fatty acid oxidation assays

    PMID:33152322

    Open questions at the time
    • Signal triggering TBK1-ACSL1 dissociation upon feeding not defined
    • Structural basis of TBK1–ACSL1 interaction unknown
  9. 2021 High

    Mapping the N-terminal 100 amino acids as necessary and sufficient for mitochondrial targeting via CPT1b interaction explained how ACSL1 couples fatty acid activation to the carnitine shuttle for β-oxidation.

    Evidence N-terminal deletion mutagenesis, co-IP with CPT1b, fatty acid oxidation and insulin resistance assays in C2C12 myotubes

    PMID:34511469

    Open questions at the time
    • Whether TBK1 binding and CPT1b binding overlap or are sequential not tested
    • Whether all CPT1 isoforms interact equivalently unknown
  10. 2021 High

    Demonstrating that ACSL1 mediates ferroptosis by incorporating conjugated linoleates into triacylglycerols defined a TAG-dependent ferroptosis pathway distinct from GPX4-inhibitor-triggered cell death.

    Evidence Genetic manipulation, lipidomics, TAG biosynthesis inhibition, lipid peroxidation and cell death assays, in vivo tumor model

    PMID:33854057

    Open questions at the time
    • How TAG-esterified PUFAs become peroxidized to execute ferroptosis not established
    • Relative contribution of ACSL1 vs other ACSL isoforms in different tissues unknown
  11. 2021 High

    Showing that Acsl1 knockout mice die with severe skin barrier defects from failed linoleic acid activation and ω-O-acylceramide synthesis revealed a non-redundant developmental role for ACSL1.

    Evidence Acsl1 whole-body KO mice, ceramide lipidomics, gene expression profiling

    PMID:34813948

    Open questions at the time
    • Whether other ACSL isoforms partially compensate in heterozygotes not tested
    • Cell-type-specific requirements in epidermis not dissected
  12. 2022 High

    Identifying CHREBP and NF-κB (p65) as direct transcriptional activators of the Acsl1 promoter in macrophages linked glucose sensing and inflammatory signals to ACSL1 induction via conserved cis-elements.

    Evidence ChIP, promoter reporter assays, CHREBP overexpression and KO bone marrow-derived macrophages, primary human monocytes

    PMID:36054206

    Open questions at the time
    • Interplay between CHREBP and NF-κB at the same promoter not resolved
    • Epigenetic regulation at these sites not explored
  13. 2023 Medium

    Demonstrating that ACSL1 promotes FSP1 N-myristoylation, stabilizing FSP1 and enabling its membrane translocation to suppress ferroptosis, revealed a second ferroptosis-related mechanism distinct from TAG incorporation.

    Evidence ACSL1 overexpression/knockdown, N-myristoylation and protein stability assays, membrane fractionation, lipid peroxidation assays in ovarian cancer cells

    PMID:36882396

    Open questions at the time
    • Whether ACSL1 directly generates myristoyl-CoA for FSP1 modification or acts indirectly not shown
    • Generalizability beyond ovarian cancer cells untested
  14. 2023 High

    Showing that PRMT1 inhibition de-represses ACSL1 via reduced H4R3me2a at its promoter, driving ferroptosis in AML cells that is reversed by ACSL1 KO, placed ACSL1 as the effector of PRMT1-regulated ferroptosis.

    Evidence PRMT1 KO and inhibitor treatment, ChIP for H4R3me2a, ACSL1 KO epistasis, lipid peroxidation assay, in vivo xenograft

    PMID:37144835

    Open questions at the time
    • Whether PRMT1 directly methylates H4R3 at the ACSL1 locus or acts through intermediary complexes not distinguished
    • Applicability beyond AML subtype not tested
  15. 2024 High

    Discovering that MCL-1 binds ACSL1 through its BH3-binding groove to stabilize the enzyme and sustain long-chain fatty acid oxidation linked anti-apoptotic BCL-2 family biology to metabolic regulation.

    Evidence Reciprocal co-IP, BH3-groove mutagenesis, Mcl1 KO, BH3-mimetic inhibitors, FAO assays in cells and mouse liver/heart

    PMID:38503284

    Open questions at the time
    • Structural details of MCL-1–ACSL1 complex unresolved
    • Whether MCL-1 binding affects ACSL1 localization or only stability unknown
  16. 2024 High

    Identifying sortilin-mediated translocation of ACSL1 from mitochondria to endolysosomes for degradation revealed a regulated turnover mechanism that controls mitochondrial fatty acid oxidation and beige fat thermogenesis.

    Evidence Sortilin KO in adipocytes, ACSL1 subcellular fractionation, AMPK/PGC1α signaling, HFD mouse model

    PMID:39232011

    Open questions at the time
    • Sorting signals on ACSL1 recognized by sortilin not mapped
    • Whether other ACSL isoforms are similarly regulated by sortilin unknown
  17. 2025 Medium

    Demonstrating that ergosterol directly binds the C-terminal ASLD1 domain of ACSL1 and allosterically stabilizes a closed, active conformation identified a sterol ligand that positively regulates enzymatic activity.

    Evidence In vitro binding assays, conformational analysis, structure-activity studies, ACSL1 KD/KO validation, β-oxidation assays

    PMID:39799570

    Open questions at the time
    • Physiological relevance of ergosterol (a fungal sterol) to mammalian ACSL1 regulation unclear
    • Whether endogenous mammalian sterols act analogously not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The specific acyl-CoA products that mediate ACSL1's activation of NF-κB/JNK signaling, the structural basis of the ACSL1–CPT1b and ACSL1–TBK1 complexes, and how TAG-incorporated PUFAs generated by ACSL1 are converted to lipid peroxides to execute ferroptosis remain unresolved.
  • No high-resolution structure of mammalian ACSL1 or its complexes
  • Lipid mediator identity downstream of ACSL1 in inflammatory signaling unknown
  • Mechanism linking ACSL1-generated TAG-PUFAs to ferroptotic peroxidation not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005739 mitochondrion 4 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-1430728 Metabolism 7 R-HSA-5357801 Programmed Cell Death 4 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3
Partners
CPT1BFATP1FATP2FSP1MCL1SORT1TBK1

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Rat ACSL1 (ACS1) purified from E. coli expression system demonstrated long-chain acyl-CoA synthetase activity with highest efficiency for saturated fatty acids with 10–18 carbons and unsaturated fatty acids including palmitoleate, oleate, and linoleate; deletion mutagenesis showed all five structural regions are required for enzymatic activity. Recombinant protein expression in E. coli, enzymatic activity assay, deletion mutagenesis European journal of biochemistry High 8973631
2000 Purified rat recombinant ACSL1 (ACS1) efficiently catalyzes thioesterification of 2-arylpropionic acid NSAIDs (ibuprofen, fenoprofen) with marked stereoselectivity for the (-)R-enantiomer, identifying ACSL1 as the major enzyme responsible for the first step of chiral inversion of these drugs. Recombinant protein purification from E. coli, in vitro enzymatic activity assay with Michaelis-Menten kinetics, stereoselectivity measurement Drug metabolism and disposition High 10725307
2010 ACSL1 and FATP1 are required for AMPK activation by adiponectin and insulin in mouse adipocytes; knockdown of either enzyme abolished the AMP/ATP ratio increase and AMPK activation, as well as stimulation of long-chain fatty acid uptake. siRNA knockdown in adipocytes, AMP/ATP ratio measurement, AMPK phosphorylation assay, fatty acid uptake assay FASEB journal High 20667975
2011 Overexpressed ACSL1 localizes to mitochondria (not plasma membrane) in 3T3-L1 adipocytes and increases acyl-CoA synthetase activity and fatty acid uptake indirectly via metabolic trapping rather than direct plasma membrane transport. Retroviral transduction for stable overexpression, confocal microscopy, subcellular fractionation, acyl-CoA synthetase activity assay, fatty acid uptake assay PloS one High 23024797
2011 Overexpression of ACSL1 in human hepatoma cells (HuH7 and HepG2) localizes to mitochondria and significantly increases acyl-CoA synthetase activity and fatty acid uptake, supporting an indirect mechanism via esterification. Overexpression in HuH7/HepG2 cells, immunofluorescence co-localization, ACS activity assay, [3H]-oleic acid and fluorescent fatty acid uptake assay, quantitative FACS International journal of medical sciences Medium 22022213
2020 TBK1 functions as a scaffolding protein (in its inactive, unphosphorylated state during fasting) to localize ACSL1 to mitochondria, channeling acyl-CoAs toward β-oxidation; loss of TBK1 shifts ACSL1 to the endoplasmic reticulum, promoting fatty acid re-esterification and hepatic lipid accumulation. Liver-specific TBK1 knockout mice, subcellular fractionation, fatty acid oxidation assay, rescue with kinase-dead TBK1 expression, Co-immunoprecipitation Cell metabolism High 33152322
2021 ACSL1 mediates ferroptosis triggered by conjugated linoleates (e.g., α-eleostearic acid) by promoting their incorporation into neutral lipids including triacylglycerols; interfering with triacylglycerol biosynthesis suppresses αESA-triggered ferroptosis but not GPX4-inhibition-triggered ferroptosis. Genetic manipulation (knockdown/overexpression), lipidomics, lipid peroxidation assay, cell death assay, pharmacological inhibition of triacylglycerol biosynthesis, in vivo tumor model Nature communications High 33854057
2021 ACSL1 N-terminal 100 amino acids are essential for mitochondrial outer membrane localization via interaction with CPT1b; ACSL1 wild type but not N-terminal deletion mutant increases fatty acid oxidation and ameliorates palmitate-induced insulin resistance in C2C12 myotubes. Deletion mutagenesis of N-terminal 100 aa, subcellular localization by microscopy, Co-immunoprecipitation with CPT1b, fatty acid oxidation assay, insulin resistance assay Molecules and cells High 34511469
2021 Acsl1 knockout in mice causes severe skin barrier defects and embryonic lethality due to failure to activate linoleic acid, resulting in reduced ω-O-acylceramide (Cer[EOS]) synthesis and accumulation of the precursor ω-hydroxy ceramide (Cer[OS]). Acsl1 knockout mouse model, lipidomics/ceramide profiling, gene expression analysis Biochimica et biophysica acta. Molecular and cell biology of lipids High 34813948
2023 ACSL1 increases N-myristoylation of ferroptosis suppressor protein 1 (FSP1), inhibiting FSP1 degradation and promoting its translocation to the cell membrane, thereby counteracting oxidative stress-induced ferroptosis in ovarian cancer cells. Genetic manipulation (ACSL1 overexpression/knockdown), N-myristoylation assay, FSP1 protein stability assay, membrane fractionation, lipid peroxidation assay Cell death discovery Medium 36882396
2020 ACSL1 activates the AMPK and Src pathways via protein myristoylation in ovarian cancer cells, converting NM cells to an HM phenotype with enhanced fatty acid beta-oxidation and increased metastasis. Shotgun proteomics, ACSL1 overexpression in NM cells, AMPK/Src pathway activation assays, lipidomics Oncogene Medium 33082557
2016 SREBP2 specifically activates a C-promoter-derived ACSL1 transcript via a sterol regulatory element (SRE) motif in the ACSL1 C-promoter; demonstrated by promoter activity assay, DNA binding assay, and SREBP2 knockdown reducing ACSL1 mRNA and protein. Promoter activity assay, EMSA/DNA binding assay, SREBP2 knockdown in HepG2, in vivo hamster/mouse models with statin or high cholesterol/fat diet The Journal of biological chemistry High 26728456
2018 Hepatic ACSL1 depletion leads to dysregulated cholesterol metabolism (hypercholesterolemia, reduced LDL receptor) and repression of bile acid biosynthetic enzyme expression; FXR activation by obeticholic acid represses ACSL1 in an FXR-dependent manner, identifying ACSL1 as a novel FXR target gene. Adenoviral shRNA-mediated hepatic ACSL1 knockdown in mice, genome-wide gene expression profiling, FXR KO mice with FXR agonist treatment Biochimica et biophysica acta. Molecular and cell biology of lipids High 30580099
2019 TNFα-induced pro-inflammatory polarization of monocytes (upregulation of CD16, CD11b, CD11c, HLA-DR, IL-1β, MCP-1) requires ACSL1 and is mediated through NF-κB; ACSL1 inhibition (triacsin C) or siRNA knockdown significantly suppresses these effects, while β-oxidation and ceramide biosynthesis inhibition do not. ACSL1 inhibitor (triacsin C), siRNA knockdown, flow cytometry, ELISA, NF-κB reporter cells, Western blot for NF-κB phosphorylation Cellular physiology and biochemistry Medium 30845379
2022 TNFα-induced MMP-9 expression in monocytic cells is mediated through ACSL1, which activates the JNK/ERK/NF-κB axis; ACSL1 inhibition or knockdown reduces TNFα-induced phosphorylation of JNK, c-Jun, ERK1/2, and NF-κB p65 and NF-κB/AP-1 activity. ACSL1 inhibitor (triacsin C), siRNA knockdown, Western blot for pathway phosphorylation, NF-κB/AP-1 reporter cells, ELISA, qRT-PCR Scientific reports Medium 37658104
2022 Transcription factor CHREBP regulates ACSL1 mRNA expression in macrophages under high glucose conditions, and NF-κB (p65/RELA) drives ACSL1 mRNA upregulation in response to LPS; both transcription factors bind and activate the Acsl1 promoter at conserved sites. ACSL1 reporter gene assay, ChIP assay, CHREBP/p65 overexpression, bone marrow-derived macrophages from CHREBP KO mice, primary human monocytes PloS one High 36054206
2024 MCL-1 binds ACSL1 through a non-conventional BH3-domain interaction with the BH3-binding hydrophobic groove of MCL-1; genetic loss of Mcl1, mutagenesis, or BH3-mimetic MCL-1 inhibitors repress long-chain (but not short-chain) fatty acid β-oxidation in cells and in mouse livers and hearts. Co-immunoprecipitation, mutagenesis of BH3 domain, Mcl1 genetic knockout, BH3-mimetic inhibitor treatment, fatty acid oxidation assay in cells and tissues Molecular cell High 38503284
2024 Sortilin (encoded by Sort1) facilitates translocation of ACSL1 from mitochondria to the endolysosomal pathway for degradation in adipocytes; sortilin depletion increases mitochondrial ACSL1, activates AMPK/PGC1α signaling, and promotes beige fat activation and fatty acid oxidation. Sortilin KO in adipocytes, ACSL1 subcellular fractionation, AMPK/PGC1α signaling assays, thermogenic gene expression, HFD mouse model Nature communications High 39232011
2023 PRMT1 inhibition (GSK3368715) or PRMT1 knockout upregulates ACSL1 in AML cells by reducing H4R3me2a histone methylation at the ACSL1 promoter, thereby promoting ferroptosis; ACSL1 knockout reverses the ferroptosis sensitivity. PRMT1 KO, GSK3368715 treatment, ChIP for H4R3me2a at ACSL1 promoter, ACSL1 KO epistasis, lipid peroxidation assay, in vivo xenograft Molecular carcinogenesis High 37144835
2024 PRMT6 interacts with STAT1 to jointly repress ACSL1 transcription; PRMT6 reduction upregulates ACSL1, increases phospholipid-PUFA production, and drives ferroptosis in diabetic nephropathy; STAT1-specific inhibitor fludarabine reduces ACSL1 expression and delays DN progression. PRMT6 KO mice, transcriptomic and lipidomic analyses, molecular biology assays for PRMT6-STAT1 interaction and ACSL1 transcription, STAT1 inhibitor treatment Cell death and differentiation Medium 39134684
2025 Ergosterol directly binds to the C-terminal acetyl-CoA synthetase-like domain 1 (ASLD1) of ACSL1, stabilizing its closed conformation and allosterically activating its activity; ergosterol is enriched in mitochondria and promotes fatty acid β-oxidation specifically through ACSL1. In vitro binding assay, conformational analysis, structure-activity relationship analysis, ACSL1 KD/KO validation, mitochondrial fractionation, β-oxidation assay Cell reports Medium 39799570
2023 ACSL1 inhibition or knockdown in macrophages suppresses palmitate-induced foamy/inflammatory phenotype by inhibiting the CD36-FABP4-p38-PPARδ signaling axis; in vivo oral administration of ACSL1 inhibitor triacsin-C in mice before acute high-fat feeding normalized inflammatory/foamy phenotype of circulating monocytes by suppressing FABP4 expression. ACSL1 pharmacological inhibition (triacsin C), siRNA knockdown, signaling pathway analysis, in vivo mouse model with oral triacsin C iScience Medium 37416456
1992 The human gene FACL1 (ACSL1, encoding palmitoyl-CoA ligase) was chromosomally mapped to chromosome region 3q13 by in situ hybridization. In situ hybridization Cytogenetics and cell genetics Medium 1531127
2023 FATP2 physically interacts with ACSL1 in NSCLC cells (shown by Co-IP); FATP2 silencing combined with ACSL1 overexpression further inhibits proliferation and lipid deposition and promotes fatty acid decomposition, indicating FATP2 regulates lipid metabolism through ACSL1. Co-immunoprecipitation, siRNA knockdown, ACSL1 overexpression (pcDNA-ACSL1), cell proliferation and lipid accumulation assays Tissue & cell Low 37172427
2024 PRMT7 catalyzes monomethylation of H4R3 (H4R3me1) at the HMGB2 promoter, enhancing HMGB2 transcription; HMGB2 then binds the ACSL1 promoter and activates ACSL1 transcription, driving ferroptosis in severe acute pancreatitis. PRMT7 overexpression/inhibition, ChIP for H4R3me1, HMGB2-ACSL1 promoter binding assay, ferroptosis assays in AR42J cells and SAP mouse model Journal of proteome research Medium 38376246
2017 NF-κB directly regulates ACSL1 transcription in liver cancer cells; the oncoprotein HBXIP acts as a coactivator with transcription factor Sp1 by binding the ACSL1 promoter to upregulate ACSL1 mRNA and protein in breast cancer cells. ChIP assay for HBXIP/Sp1 at ACSL1 promoter, HBXIP overexpression/knockdown, NF-κB inhibitor (PDTC), lipid droplet and triglyceride quantification Biochemical and biophysical research communications Medium 28132807 28359761
2022 ACSL1 overexpression in K562 CML cells induces cellular senescence and inhibits cell growth via the SIRT1/p53/p21 axis; ACSL1 knockdown reverses imatinib-induced senescence. ACSL1 overexpression/knockdown, cell cycle analysis, senescence assays, Western blot for SIRT1/p53/p21 pathway, in vivo xenograft Scientific reports Medium 36289272
2022 ACSL1 knockdown in mice (via AAV9) promotes cardiomyocyte cell cycle progression from G0 to G2, enhances myocardial regeneration, and correlates with AKT activation and FOXO1 nuclear exclusion. AAV9-mediated ACSL1 knockdown in mice, RNA-seq of mouse hearts at different developmental ages, cell cycle analysis, AKT/FOXO1 signaling assays, myocardial infarction model Life sciences Medium 35122795

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 The acyl-CoA synthetase encoded by LACS2 is essential for normal cuticle development in Arabidopsis. The Plant cell 273 14973169
2021 Ferroptotic cell death triggered by conjugated linolenic acids is mediated by ACSL1. Nature communications 204 33854057
2008 ACSL1, AGPAT6, FABP3, LPIN1, and SLC27A6 are the most abundant isoforms in bovine mammary tissue and their expression is affected by stage of lactation. The Journal of nutrition 182 18492828
2020 TANK-Binding Kinase 1 Regulates the Localization of Acyl-CoA Synthetase ACSL1 to Control Hepatic Fatty Acid Oxidation. Cell metabolism 105 33152322
2010 Insertional mutant analysis reveals that long-chain acyl-CoA synthetase 1 (LACS1), but not LACS8, functionally overlaps with LACS9 in Arabidopsis seed oil biosynthesis. The Plant journal : for cell and molecular biology 103 21143684
2011 Overexpression of CD36 and acyl-CoA synthetases FATP2, FATP4 and ACSL1 increases fatty acid uptake in human hepatoma cells. International journal of medical sciences 102 22022213
2014 MiR-205 modulates abnormal lipid metabolism of hepatoma cells via targeting acyl-CoA synthetase long-chain family member 1 (ACSL1) mRNA. Biochemical and biophysical research communications 97 24462768
2011 The rno-miR-34 family is upregulated and targets ACSL1 in dimethylnitrosamine-induced hepatic fibrosis in rats. The FEBS journal 94 21366874
2011 Transcriptional and functional analysis of galactooligosaccharide uptake by lacS in Lactobacillus acidophilus. Proceedings of the National Academy of Sciences of the United States of America 78 22006318
2023 ACSL1-induced ferroptosis and platinum resistance in ovarian cancer by increasing FSP1 N-myristylation and stability. Cell death discovery 73 36882396
2012 Overexpressed FATP1, ACSVL4/FATP4 and ACSL1 increase the cellular fatty acid uptake of 3T3-L1 adipocytes but are localized on intracellular membranes. PloS one 71 23024797
1997 Transcriptional control of the yeast acetyl-CoA synthetase gene, ACS1, by the positive regulators CAT8 and ADR1 and the pleiotropic repressor UME6. Molecular microbiology 68 9427394
1996 Biochemical studies of two rat acyl-CoA synthetases, ACS1 and ACS2. European journal of biochemistry 64 8973631
2020 ACSL1 affects Triglyceride Levels through the PPARγ Pathway. International journal of medical sciences 63 32218693
2010 Activation of AMP-activated protein kinase signaling pathway by adiponectin and insulin in mouse adipocytes: requirement of acyl-CoA synthetases FATP1 and Acsl1 and association with an elevation in AMP/ATP ratio. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 62 20667975
2023 TNFα induces matrix metalloproteinase-9 expression in monocytic cells through ACSL1/JNK/ERK/NF-kB signaling pathways. Scientific reports 59 37658104
2017 Aspirin suppresses the abnormal lipid metabolism in liver cancer cells via disrupting an NFκB-ACSL1 signaling. Biochemical and biophysical research communications 51 28359761
2020 Metabolic reprogramming of ovarian cancer involves ACSL1-mediated metastasis stimulation through upregulated protein myristoylation. Oncogene 50 33082557
2016 MicroRNA Bta-miR-181a regulates the biosynthesis of bovine milk fat by targeting ACSL1. Journal of dairy science 50 26971144
2010 Gene-nutrient interactions with dietary fat modulate the association between genetic variation of the ACSL1 gene and metabolic syndrome. Journal of lipid research 50 20176858
1995 Carbon source-dependent regulation of the acetyl-coenzyme A synthetase-encoding gene ACS1 from Saccharomyces cerevisiae. Gene 49 7642141
2015 ACSL1 Is Associated With Fetal Programming of Insulin Sensitivity and Cellular Lipid Content. Molecular endocrinology (Baltimore, Md.) 47 25915184
2011 Arabidopsis long-chain acyl-CoA synthetase 1 (LACS1), LACS2, and LACS3 facilitate fatty acid uptake in yeast. Plant physiology and biochemistry : PPB 47 22153237
2017 HBXIP up-regulates ACSL1 through activating transcriptional factor Sp1 in breast cancer. Biochemical and biophysical research communications 46 28132807
1999 An allele of the ripening-specific 1-aminocyclopropane-1-carboxylic acid synthase gene (ACS1) in apple fruit with a long storage life. Plant physiology 46 10198088
1997 Expression characteristics of OS-ACS1 and OS-ACS2, two members of the 1-aminocyclopropane-1-carboxylate synthase gene family in rice (Oryza sativa L. cv. Habiganj Aman II) during partial submergence. Plant molecular biology 45 9037160
1997 The Saccharomyces cerevisiae acetyl-coenzyme A synthetase encoded by the ACS1 gene, but not the ACS2-encoded enzyme, is subject to glucose catabolite inactivation. FEMS microbiology letters 43 9252575
2024 Anti-apoptotic MCL-1 promotes long-chain fatty acid oxidation through interaction with ACSL1. Molecular cell 41 38503284
2023 PRMT1 inhibition promotes ferroptosis sensitivity via ACSL1 upregulation in acute myeloid leukemia. Molecular carcinogenesis 41 37144835
2020 Effects of overexpression of ACSL1 gene on the synthesis of unsaturated fatty acids in adipocytes of bovine. Archives of biochemistry and biophysics 41 33098867
2019 TNF-α Induces a Pro-Inflammatory Phenotypic Shift in Monocytes through ACSL1: Relevance to Metabolic Inflammation. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 41 30845379
2020 Methyl Jasmonate Enhances Ethylene Synthesis in Kiwifruit by Inducing NAC Genes That Activate ACS1. Journal of agricultural and food chemistry 38 32101430
2011 Association of an ACSL1 gene variant with polyunsaturated fatty acids in bovine skeletal muscle. BMC genetics 38 22078495
2021 Inhibiting ACSL1-Related Ferroptosis Restrains Murine Coronavirus Infection. Viruses 35 34960652
2016 SREBP2 Activation Induces Hepatic Long-chain Acyl-CoA Synthetase 1 (ACSL1) Expression in Vivo and in Vitro through a Sterol Regulatory Element (SRE) Motif of the ACSL1 C-promoter. The Journal of biological chemistry 35 26728456
2006 The involvement of 1-aminocyclopropane-1-carboxylic acid synthase isogene, Pp-ACS1, in peach fruit softening. Journal of experimental botany 35 16531466
2024 The PRMT6/STAT1/ACSL1 axis promotes ferroptosis in diabetic nephropathy. Cell death and differentiation 34 39134684
2019 ACSL1 Regulates TNFα-Induced GM-CSF Production by Breast Cancer MDA-MB-231 Cells. Biomolecules 34 31581558
2015 MicroRNA-34a Promotes Hepatic Stellate Cell Activation via Targeting ACSL1. Medical science monitor : international medical journal of experimental and clinical research 33 26437572
1995 Characterization of two members (ACS1 and ACS3) of the 1-aminocyclopropane-1-carboxylate synthase gene family of Arabidopsis thaliana. Gene 33 8566772
2022 Targeting ACSL1 promotes cardiomyocyte proliferation and cardiac regeneration. Life sciences 31 35122795
1999 acs1 of Haemophilus influenzae type a capsulation locus region II encodes a bifunctional ribulose 5-phosphate reductase- CDP-ribitol pyrophosphorylase. Journal of bacteriology 31 10094675
2023 RBM45 reprograms lipid metabolism promoting hepatocellular carcinoma via Rictor and ACSL1/ACSL4. Oncogene 30 38040804
2020 The function of SNHG7/miR-449a/ACSL1 axis in thyroid cancer. Journal of cellular biochemistry 30 31961004
2007 Molecular characterisation of Lac s 1, the major allergen from lettuce (Lactuca sativa). Molecular immunology 30 17349693
2019 The inhibition of Nrf2 accelerates renal lipid deposition through suppressing the ACSL1 expression in obesity-related nephropathy. Renal failure 29 31488013
2008 Characterization of transcriptional profiles of MA-ACS1 and MA-ACO1 genes in response to ethylene, auxin, wounding, cold and different photoperiods during ripening in banana fruit. Journal of plant physiology 28 18554749
2004 Inheritance of the Md-ACS1 gene and its relationship to fruit softening in apple ( Malus x domestica Borkh.). TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 27 14968302
2021 ACSL1 Inhibits ALV-J Replication by IFN-Ⅰ Signaling and PI3K/Akt Pathway. Frontiers in immunology 26 34777393
2021 Short Chain Fatty Acid Acetate Increases TNFα-Induced MCP-1 Production in Monocytic Cells via ACSL1/MAPK/NF-κB Axis. International journal of molecular sciences 24 34299302
2015 Regulation of Acetate Metabolism and Acetyl Co-a Synthetase 1 (ACS1) Expression by Methanol Expression Regulator 1 (Mxr1p) in the Methylotrophic Yeast Pichia pastoris. The Journal of biological chemistry 22 26663080
2023 CircDOCK7 facilitates the proliferation and adipogenic differentiation of chicken abdominal preadipocytes through the gga-miR-301b-3p/ACSL1 axis. Journal of animal science and biotechnology 21 37408086
2023 miR397-LACs mediated cadmium stress tolerance in Arabidopsis thaliana. Plant molecular biology 21 37566350
2023 ACSL1 is a key regulator of inflammatory and macrophage foaming induced by short-term palmitate exposure or acute high-fat feeding. iScience 20 37416456
2005 RP-ACS1, a flooding-induced 1-aminocyclopropane-1-carboxylate synthase gene of Rumex palustris, is involved in rhythmic ethylene production. Journal of experimental botany 20 15642709
1996 The lactose transporter in Leuconostoc lactis is a new member of the LacS subfamily of galactoside-pentose-hexuronide translocators. Applied and environmental microbiology 20 8633855
2024 The Diagnostic Value of ACSL1, ACSL4, and ACSL5 and the Clinical Potential of an ACSL Inhibitor in Non-Small-Cell Lung Cancer. Cancers 19 38539505
2018 Identification of a novel function of hepatic long-chain acyl-CoA synthetase-1 (ACSL1) in bile acid synthesis and its regulation by bile acid-activated farnesoid X receptor. Biochimica et biophysica acta. Molecular and cell biology of lipids 19 30580099
2015 Age-related difference in the sleep pressure-lowering effect between an angiotensin II receptor blocker and a calcium channel blocker in Asian hypertensives: the ACS1 Study. Hypertension (Dallas, Tex. : 1979) 19 25646296
2012 Expression and genome polymorphism of ACSL1 gene in different pig breeds. Molecular biology reports 17 22714915
2025 Ergosterol alleviates hepatic steatosis and insulin resistance via promoting fatty acid β-oxidation by activating mitochondrial ACSL1. Cell reports 16 39799570
2021 MiR-34c promotes hepatic stellate cell activation and Liver Fibrogenesis by suppressing ACSL1 expression. International journal of medical sciences 16 33437196
2021 An Essential Role of the N-Terminal Region of ACSL1 in Linking Free Fatty Acids to Mitochondrial β-Oxidation in C2C12 Myotubes. Molecules and cells 16 34511469
2004 The role of cis-acting sequences governing catabolite repression control of lacS expression in the archaeon Sulfolobus solfataricus. Genetics 16 15342498
2000 Thioesterification of 2-arylpropionic acids by recombinant acyl-coenzyme A synthetases (ACS1 and ACS2). Drug metabolism and disposition: the biological fate of chemicals 16 10725307
2022 ACSL1 promotes imatinib-induced chronic myeloid leukemia cell senescence by regulating SIRT1/p53/p21 pathway. Scientific reports 15 36289272
2012 A Ser/Thr protein kinase phosphorylates MA-ACS1 (Musa acuminata 1-aminocyclopropane-1-carboxylic acid synthase 1) during banana fruit ripening. Planta 15 22419220
2025 ACSL1 Aggravates Thromboinflammation by LPC/LPA Metabolic Axis in Hyperlipidemia Associated Myocardial Ischemia-Reperfusion Injury. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 14 39853712
2024 ACSL1-Mediated Fatty Acid β-Oxidation Enhances Metastasis and Proliferation in Endometrial Cancer. Frontiers in bioscience (Landmark edition) 14 38420815
2022 Transcriptional regulation of Acsl1 by CHREBP and NF-kappa B in macrophages during hyperglycemia and inflammation. PloS one 14 36054206
2005 The doubly phosphorylated form of HPr, HPr(Ser~P)(His-P), is abundant in exponentially growing cells of Streptococcus thermophilus and phosphorylates the lactose transporter LacS as efficiently as HPr(His~P). Applied and environmental microbiology 14 15746339
2025 Semaglutide Reprograms Macrophages via the GLP-1R/PPARG/ACSL1 Pathway to Suppress Papillary Thyroid Carcinoma Growth. The Journal of clinical endocrinology and metabolism 13 39908200
2024 Sortilin-mediated translocation of mitochondrial ACSL1 impairs adipocyte thermogenesis and energy expenditure in male mice. Nature communications 13 39232011
2022 MiR-218-5p Affects Subcutaneous Adipogenesis by Targeting ACSL1, a Novel Candidate for Pig Fat Deposition. Genes 13 35205304
2019 Ethylene Response of Plum ACC Synthase 1 (ACS1) Promoter is Mediated through the Binding Site of Abscisic Acid Insensitive 5 (ABI5). Plants (Basel, Switzerland) 13 31052513
2019 The Molecular Characteristics of the FAM13A Gene and the Role of Transcription Factors ACSL1 and ASCL2 in Its Core Promoter Region. Genes 13 31795267
2003 Phosphorylation of Streptococcus salivarius lactose permease (LacS) by HPr(His ~ P) and HPr(Ser-P)(His ~ P) and effects on growth. Journal of bacteriology 13 14617640
1999 Expression characteristics of CS-ACS1, CS-ACS2 and CS-ACS3, three members of the 1-aminocyclopropane-1-carboxylate synthase gene family in cucumber (Cucumis sativus L.) fruit under carbon dioxide stress. Plant & cell physiology 13 10202812
2023 ACSL1, CH25H, GPCPD1, and PLA2G12A as the potential lipid-related diagnostic biomarkers of acute myocardial infarction. Aging 12 36863716
2023 FATP2 regulates non-small cell lung cancer by mediating lipid metabolism through ACSL1. Tissue & cell 12 37172427
2022 CircPDHX promotes prostate cancer cell progression in vitro and tumor growth in vivo via miR-497-5p/ACSL1 axis. Biochemical and biophysical research communications 12 35777132
2009 The 5' untranslated region of the VR-ACS1 mRNA acts as a strong translational enhancer in plants. Transgenic research 12 19816782
2024 ACSL1 improves pulmonary fibrosis by reducing mitochondrial damage and activating PINK1/Parkin mediated mitophagy. Scientific reports 10 39489819
2023 Transcriptional Regulation Associated with Subcutaneous Adipogenesis in Porcine ACSL1 Gene. Biomolecules 10 37509093
2022 Novel Insight Into the Role of ACSL1 Gene in Milk Production Traits in Buffalo. Frontiers in genetics 10 35734439
2022 Increased Lipids in Chlamydomonas reinhardtii by Multiple Regulations of DOF, LACS2, and CIS1. International journal of molecular sciences 10 36077572
2020 Polymorphisms of the ACSL1 Gene Influence Milk Production Traits and Somatic Cell Score in Chinese Holstein Cows. Animals : an open access journal from MDPI 10 33287296
2025 Stevia rebaudiana root polysaccharide modulates liver metabolism, bile acid, and gut microbiota improving HFD-induced NAFLD: Potential roles of ACSL1 and FADS2. Phytomedicine : international journal of phytotherapy and phytopharmacology 9 40220428
2021 Interference with ACSL1 gene in bovine adipocytes: Transcriptome profiling of circRNA related to unsaturated fatty acid production. Genomics 9 34601049
2021 Interference With ACSL1 Gene in Bovine Adipocytes: Transcriptome Profiling of mRNA and lncRNA Related to Unsaturated Fatty Acid Synthesis. Frontiers in veterinary science 9 34977220
2019 The dependence of leaf senescence on the balance between 1-aminocyclopropane-1-carboxylate acid synthase 1 (ACS1)-catalysed ACC generation and nitric oxide-associated 1 (NOS1)-dependent NO accumulation in Arabidopsis. Plant biology (Stuttgart, Germany) 9 30734982
2015 Exceptional longevity and muscle and fitness related genotypes: a functional in vitro analysis and case-control association replication study with SNPs THRH rs7832552, IL6 rs1800795, and ACSL1 rs6552828. Frontiers in aging neuroscience 9 25999849
2012 Acyl coenzyme A synthetase long-chain 1 (ACSL1) gene polymorphism (rs6552828) and elite endurance athletic status: a replication study. PloS one 9 22829935
2006 Tissue-cell- and species-specific expression of gonadotropin-regulated long chain acyl-CoA synthetase (GR-LACS) in gonads, adrenal and brain. Identification of novel forms in the brain. The Journal of steroid biochemistry and molecular biology 9 16469493
2024 Polystyrene microplastics interaction and influence on the growth kinetics and metabolism of tilapia gut probiotic Bacillus tropicus ACS1. Environmental science. Processes & impacts 8 37990603
2024 PRMT7-Dependent Transcriptional Activation of Hmgb2 Aggravates Severe Acute Pancreatitis by Promoting Acsl1-Induced Ferroptosis. Journal of proteome research 8 38376246
2023 Genome-Wide Analysis and Functional Characterization of LACS Gene Family Associated with Lipid Synthesis in Cotton (Gossypium spp.). International journal of molecular sciences 8 37239883
2022 Liraglutide Exerts Protective Effects by Downregulation of PPARγ, ACSL1 and SREBP-1c in Huh7 Cell Culture Models of Non-Alcoholic Steatosis and Drug-Induced Steatosis. Current issues in molecular biology 8 36005135
2021 Acsl1 is essential for skin barrier function through the activation of linoleic acid and biosynthesis of ω-O-acylceramide in mice. Biochimica et biophysica acta. Molecular and cell biology of lipids 8 34813948
1992 Chromosomal localization of the human gene for palmitoyl-CoA ligase (FACL1). Cytogenetics and cell genetics 8 1531127