Affinage

ACSL5

Long-chain-fatty-acid--CoA ligase 5 · UniProt Q9ULC5

Length
683 aa
Mass
76.0 kDa
Annotated
2026-04-28
55 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ACSL5 is a mitochondria-associated long-chain acyl-CoA synthetase that activates C10–C18 fatty acids—with preference for C16–C18 unsaturated species—to their CoA thioesters, channeling them predominantly toward β-oxidation and thereby governing cellular energy metabolism, lipid homeostasis, and fat absorption (PMID:9722683, PMID:17761945, PMID:26977393). In the intestine, ACSL5 is the dominant ACSL isoform; its loss reduces dietary fat absorption, increases distal intestinal fatty acid delivery to enteroendocrine cells, and elevates GLP-1/PYY secretion to suppress food intake, protecting against diet-induced obesity (PMID:26977393, PMID:38499083, PMID:33106515). ACSL5 activity is regulated post-translationally by SIRT6-mediated deacetylation (enhancing activity) and by USP29- and OTUB1-mediated K48-linked deubiquitination that prevents proteasomal degradation, and transcriptionally by ERK/oncostatin M, STAT3, OC2/ONECUT2, IRF-1, and the JAB1–CRL4B repressor complex (PMID:36208627, PMID:39355870, PMID:40280245, PMID:17761945, PMID:39557186, PMID:32129880, PMID:41388188). In cancer, ACSL5 modulates MHC-I antigen presentation to sensitize tumors to immune checkpoint blockade, promotes cellular senescence through acetyl-CoA-driven 53BP1 acetylation, confers ferroptosis resistance, and facilitates metastatic adaptation via COX2/PGE2 signaling (PMID:38350448, PMID:40595416, PMID:39927464, PMID:41570334).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1998 High

    Establishing the enzymatic identity of ACSL5: purified recombinant protein demonstrated it is a long-chain acyl-CoA synthetase with a distinct substrate profile (C10–C18, preferring C16–C18 unsaturated fatty acids), distinguishing it from other ACSL family members.

    Evidence Recombinant overexpression in E. coli, purification to homogeneity, enzymatic activity assays with diverse fatty acid substrates

    PMID:9722683

    Open questions at the time
    • No determination of subcellular localization
    • No tissue expression data beyond initial cloning
    • Kinetic parameters for all substrates not fully resolved
  2. 2007 High

    Linking ACSL5 to fatty acid β-oxidation and transcriptional regulation: oncostatin M induces ACSL5 via ERK signaling in hepatocytes, and ACSL5 overexpression preferentially channels fatty acids into β-oxidation rather than triglyceride storage, a function abolished by siRNA knockdown.

    Evidence Transcriptional reporter assays, siRNA knockdown, overexpression in HepG2 cells, fatty acid oxidation assays, in vivo hamster model

    PMID:17761945

    Open questions at the time
    • Mechanism by which ACSL5 preferentially directs acyl-CoA to β-oxidation versus other fates not defined
    • ERK-responsive cis-regulatory element not mapped
  3. 2011 Medium

    Revealing a pro-apoptotic role in lymphocytes: ACSL5 silencing reduced activation-induced apoptosis and downregulated FAS/FASLG/TNF expression in T cells, expanding ACSL5 function beyond metabolic channeling.

    Evidence siRNA knockdown in Jurkat T cells, apoptosis assays, RT-qPCR for death receptor ligands

    PMID:22163040

    Open questions at the time
    • Mechanism linking acyl-CoA production to death receptor gene transcription unknown
    • Not confirmed in primary T cells
    • No lipid metabolite analysis
  4. 2014 Medium

    Connecting ACSL5 to mitochondrial proteome remodeling: ACSL5 overexpression specifically upregulated mitochondrial mortalin (HSPA9) through altered acyl-CoA/sphingolipid metabolism in a p53-dependent manner, linking ACSL5 activity to mitochondrial stress responses.

    Evidence Mitochondrial proteomics, Western blot, siRNA knockdown, tandem mass spectrometry lipidomics in CaCo2 cells

    PMID:24770931

    Open questions at the time
    • Direct mechanism for sphingolipid-driven mortalin induction not established
    • Single cell line
    • Functional consequence of mortalin upregulation not tested
  5. 2016 High

    Establishing ACSL5 as the dominant intestinal ACSL and a regulator of whole-body energy metabolism: ACSL5-knockout mice exhibited ~80% loss of jejunal ACSL activity, delayed fat absorption, reduced adiposity, improved insulin sensitivity, and massively elevated FGF21, while a linked genetic study demonstrated that a functional splice variant (exon 20 skipping) alters ACSL5 activity.

    Evidence Whole-body knockout mouse with indirect calorimetry, oral fat gavage, insulin tolerance tests, FGF21 quantification; eQTL and exon-skipping assay for splice variant

    PMID:26977393 PMID:27189022

    Open questions at the time
    • Whether the metabolic phenotype is entirely intestine-autonomous was not resolved (whole-body KO)
    • Direct substrates and acyl-CoA species altered in intestinal epithelium not profiled
  6. 2016 High

    Linking the TCF7L2 type 2 diabetes risk locus to ACSL5 regulation: CRISPR deletion of the rs7903146-containing regulatory element reduced ACSL5 mRNA up to 30-fold and abolished chromatin contacts with the ACSL5 promoter, establishing ACSL5 as a target gene of this diabetes-associated variant.

    Evidence CRISPR/Cas9 deletion, 4C and Capture-C chromatin conformation capture, gene expression profiling

    PMID:27539148

    Open questions at the time
    • Functional consequence of reduced ACSL5 in the cell types relevant to diabetes (β-cells, intestine) not tested
    • Whether ACSL5 reduction mediates the diabetes risk phenotype not proven
  7. 2018 Medium

    Demonstrating isoform-specific localization and function: the shorter 683 aa ACSL5 isoform (favored by the rs2419621 T allele) preferentially localizes to mitochondria and drives greater fatty acid oxidation and mitochondrial respiration compared to the longer isoform.

    Evidence 14C palmitate oxidation in C2C12 myoblasts, subcellular localization, high-resolution respirometry on human muscle biopsies

    PMID:29605434

    Open questions at the time
    • Structural basis for differential mitochondrial targeting of the two isoforms not defined
    • Small human sample size
  8. 2020 Medium

    Confirming ACSL5 is essential for intestinal fat absorption in a natural loss-of-function model: a homozygous deletion encompassing ACSL5 in dogs caused complete loss of jejunal ACSL5 expression, steatorrhea, and stunted growth, phenocopying the mouse knockout.

    Evidence GWAS, whole transcriptomic sequencing, autosomal recessive inheritance confirmation in Australian Kelpie dogs

    PMID:33106515

    Open questions at the time
    • Deletion also removes ZDHHC6, so contribution of ZDHHC6 loss to phenotype not excluded
    • No biochemical characterization of residual ACSL activity
  9. 2020 Medium

    Identifying a direct transcriptional activator in gastric tissue: ONECUT2 binds the ACSL5 promoter and activates its transcription, with OC2 promoter hypomethylation driving ACSL5 upregulation in intestinal metaplasia and gastric cancer.

    Evidence ChIP-seq, RNA-seq, OC2 knockdown/overexpression, bisulfite sequencing, xenograft tumorigenesis

    PMID:32129880

    Open questions at the time
    • Whether ACSL5 is the key downstream mediator of OC2 oncogenic effects not formally tested by ACSL5 rescue
    • Mechanism linking ACSL5 to gastric tumorigenesis not defined
  10. 2022 High

    Establishing a post-translational activation mechanism: SIRT6, triggered by palmitic acid binding, translocates to the cytoplasm and directly deacetylates ACSL5, enhancing its enzymatic activity; a deacetylation-mimic ACSL5 mutant rescues NAFLD in Sirt6-deficient livers.

    Evidence Co-immunoprecipitation, deacetylation assays, subcellular fractionation, hepatic overexpression/depletion in mice, deacetylation-mimic rescue, human NASH tissue analysis

    PMID:36208627

    Open questions at the time
    • Specific acetylation sites on ACSL5 targeted by SIRT6 not fully mapped
    • Whether SIRT6-ACSL5 axis operates in non-hepatic tissues not tested
  11. 2024 High

    Resolving the intestine-autonomous mechanism: intestine-specific ACSL5 knockout protected mice from diet-induced obesity exclusively through reduced food intake; loss of ACSL5 increased distal intestinal fatty acid content, elevated postprandial GLP-1/PYY, and GLP-1 receptor antagonism partially reversed the anorectic phenotype.

    Evidence Tamoxifen-inducible intestine-specific Cre knockout, metabolic phenotyping, GLP-1/PYY measurement, GLP-1R antagonist rescue

    PMID:38499083

    Open questions at the time
    • How unesterified fatty acids reaching the distal intestine stimulate enteroendocrine cells not molecularly defined
    • Whether ACSL5 inhibition in humans would recapitulate anorexigenic effects unknown
  12. 2024 High

    Expanding ACSL5 into cancer immunology: ACSL5 enhances MHC-I antigen presentation, sensitizing tumors to PD-1 blockade and CD8+ T cell killing; the trans fatty acid elaidic acid phenocopies ACSL5 to boost MHC-I expression and suppress tumor growth in vivo.

    Evidence In vivo tumor models with PD-1 blockade, CD8+ T cell cytotoxicity assays, ACSL5 substrate screening, dietary elaidic acid supplementation

    PMID:38350448

    Open questions at the time
    • Lipid species mediating MHC-I upregulation not identified
    • Whether effect generalizes across tumor types not established
  13. 2024 High

    Defining a ubiquitin-mediated stability control mechanism: USP29 directly binds and deubiquitinates ACSL5 via K48-linked chains, preventing proteasomal degradation; loss of USP29 reduces ACSL5 levels and β-oxidation, worsening hepatic steatosis, while USP29 overexpression is hepatoprotective in an ACSL5-dependent manner.

    Evidence Co-immunoprecipitation, K48-linkage-specific ubiquitination assays, USP29 KO and OE in mice and hepatocytes, ACSL5 rescue experiments

    PMID:39355870

    Open questions at the time
    • Specific ubiquitin sites on ACSL5 not mapped
    • E3 ligase responsible for K48 ubiquitination of ACSL5 not identified
  14. 2025 High

    A second deubiquitinase (OTUB1) was identified as a direct ACSL5 stabilizer by mass spectrometry, paralleling USP29; OTUB1-mediated ACSL5 stabilization improves fatty acid oxidation and protects against APAP-induced liver injury in an ACSL5-dependent manner.

    Evidence Mass spectrometry substrate identification, Co-IP, deubiquitination assay, OTUB1 OE/KD in mice and hepatocytes, ACSL5 co-depletion rescue

    PMID:40280245

    Open questions at the time
    • Whether USP29 and OTUB1 act redundantly or in different contexts not resolved
    • Structural basis of OTUB1–ACSL5 interaction unknown
  15. 2025 Medium

    In cancer, ACSL5 operates at a metabolic–signaling nexus: it promotes senescence in bladder cancer by generating acetyl-CoA that acetylates 53BP1-K1360 to activate the p53–p21 axis; in colorectal cancer it stabilizes MDM2 by competing with MIB1, suppressing p53, and activates glycolysis (PGAM1) and TCA cycle (IDH2); in rhabdomyosarcoma it confers ferroptosis resistance downstream of AURKB/NPM1/SP1; and in metastatic breast cancer it fuels COX2/PGE2 signaling via palmitoylation to activate PI3K/AKT and ERK through EP4.

    Evidence ACSL5 OE/KD across bladder, colorectal, rhabdomyosarcoma, and breast cancer cell lines; acetyl-CoA and 53BP1 acetylation assays; Co-IP for MIB1–MDM2 competition; ferroptosis and apoptosis assays; COX2/PGE2 measurement; in vivo xenograft and metastasis models

    PMID:39927464 PMID:40595416 PMID:41355704 PMID:41570334

    Open questions at the time
    • Many cancer-specific mechanisms reported by single labs and not yet independently replicated
    • Whether these diverse downstream effects all stem from acyl-CoA channeling or involve non-catalytic ACSL5 functions is unclear
    • Context-dependent tumor-suppressive versus oncogenic roles not reconciled
  16. 2025 Medium

    Additional transcriptional regulators of ACSL5 identified: STAT3 activates ACSL5 under diabetic conditions to promote lipoapoptosis in kidney tubular cells; JAB1–CRL4B represses ACSL5 at its promoter in breast cancer to suppress fatty acid metabolism; IRF-1 induces ACSL5 in kidney tubular cells to maintain ATP production and modulate the lipidome.

    Evidence ChIP for CRL4B at ACSL5 promoter; STAT3 promoter activation assay and KD/OE rescue in kidney cells; transcriptomic/lipidomic analysis with IRF-1 manipulation

    PMID:39557186 PMID:40546938 PMID:41388188

    Open questions at the time
    • Direct STAT3 binding to ACSL5 promoter not shown by ChIP
    • Relative importance of these regulators across tissues not established
    • Whether these inputs converge on the same or different ACSL5 isoforms is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis for ACSL5's substrate selectivity and mitochondrial targeting; the identity of the E3 ubiquitin ligase(s) that mark ACSL5 for K48-linked degradation; the specific acyl-CoA or lipid species mediating ACSL5's effects on MHC-I presentation, ferroptosis, and senescence; whether ACSL5 has non-catalytic scaffolding functions (e.g., MDM2 stabilization); and whether pharmacological ACSL5 modulation can safely replicate the anorexigenic or immunomodulatory effects observed in animal models.
  • No crystal structure or cryo-EM model of ACSL5
  • E3 ligase targeting ACSL5 for ubiquitination not identified
  • No selective pharmacological inhibitor or activator reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 2 GO:0016740 transferase activity 1
Localization
GO:0005739 mitochondrion 3
Pathway
R-HSA-1430728 Metabolism 7 R-HSA-162582 Signal Transduction 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-168256 Immune System 1
Partners
HSPA9MDM2MIB1OTUB1SIRT6USP29

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 ACSL5 (rat ACS5) is a novel long-chain acyl-CoA synthetase that activates a wide range of saturated fatty acids (C10–C18) and shows a distinct preference for C16–C18 unsaturated fatty acids (oleate, arachidonate, EPA, DHA) compared to ACS1/ACS2, as demonstrated by purification from E. coli and enzymatic characterization. Recombinant protein overexpression in E. coli, purification to homogeneity, enzymatic activity assay with various fatty acid substrates Journal of biochemistry High 9722683
2007 Oncostatin M (OM) activates transcription of ACSL5 (and ACSL3) in hepatocytes through the ERK signaling pathway, and overexpression of ACSL5 alone partitions fatty acids into β-oxidation, reducing triglyceride accumulation; siRNA knockdown of ACSL5 abrogates OM-enhanced fatty acid oxidation. Transcriptional reporter assays, siRNA knockdown, overexpression in HepG2 cells, fatty acid oxidation assays, in vivo hamster model Arteriosclerosis, thrombosis, and vascular biology High 17761945
2016 Whole-body ACSL5 knockout mice show ~80% reduction in jejunal ACSL activity, reduced fat mass, increased energy expenditure, improved insulin sensitivity, delayed dietary triglyceride absorption after olive oil gavage, and markedly elevated hepatic and serum FGF21 levels (~16-fold and ~13-fold, respectively), establishing ACSL5 as a key regulator of intestinal fat absorption and whole-body energy metabolism. Conditional/whole-body knockout mouse model, indirect calorimetry, insulin tolerance test, oral fat gavage/triglyceride appearance assay, ACSL activity assays, FGF21 quantification Molecular metabolism High 26977393
2016 The TCF7L2 type 2 diabetes risk variant rs7903146 resides in a regulatory element that physically contacts the ACSL5 promoter (demonstrated by 4C and Capture-C); CRISPR deletion of this region reduces ACSL5 mRNA up to 30-fold and abolishes chromatin contacts with the ACSL5 promoter, identifying ACSL5 as the gene under the influence of this diabetes-associated variant. CRISPR/Cas9 deletion, global gene expression analysis, circularized chromosome conformation capture (4C), Capture-C, Western blot Diabetologia High 27539148
2018 The rs2419621 T allele of ACSL5 is associated with higher levels of the 683 aa ACSL5 protein isoform, which localizes predominantly to mitochondria (vs. the 739 aa isoform), and drives greater fatty acid oxidation in C2C12 myoblasts overexpressing human ACSL5, in primary rectus abdominis myotubes from T-allele carriers, and increased complex I/II respiration in vastus lateralis biopsies. 14C palmitic acid oxidation, Western blot, subcellular localization by overexpression in C2C12 cells, high-resolution respirometry on muscle biopsies Metabolism: clinical and experimental Medium 29605434
2022 SIRT6 binds saturated fatty acids (especially palmitic acid), which triggers its nuclear export to the cytoplasm where it directly deacetylates ACSL5, enhancing ACSL5-mediated fatty acid β-oxidation; hepatic overexpression of a deacetylated ACSL5 mimic attenuates NAFLD in Sirt6 liver-specific knockout mice, and NASH tissues show reduced cytoplasmic SIRT6 and increased ACSL5 acetylation. Co-immunoprecipitation, subcellular fractionation, deacetylation assays, hepatic overexpression/depletion in mouse models, deacetylation-mimic rescue experiments, patient tissue analysis Molecular cell High 36208627
2011 siRNA-mediated silencing of ACSL5 in Jurkat T cells decreases PMA/ionomycin-induced apoptosis to control levels and reduces mRNA expression of FAS, FASLG, and TNF, establishing a pro-apoptotic role for ACSL5 in T lymphocytes. siRNA knockdown, apoptosis assay, quantitative RT-PCR for apoptosis-related genes PloS one Medium 22163040
2014 ACSL5 overexpression in CaCo2 cells induces ~2-fold increase of mortalin (HSPA9) specifically in mitochondria (not cytoplasm), mediated through disturbance of acyl-CoA/sphingolipid metabolism; this mitochondrial mortalin upregulation is dependent on wild-type TP53 status and is observed in normal intestinal mucosa with an increasing gradient from crypt to villus tip. Mitochondrial proteomics of ACSL5 transfectants vs. CaCo2 controls, Western blot, siRNA knockdown, tandem mass spectrometry lipid analysis, immunohistochemistry of normal mucosa and adenocarcinomas Cell and tissue research Medium 24770931
2016 A functional variant rs2256368:A>G causes skipping of exon 20 in ACSL5 transcripts (ACSL5-Δ20) in ~20–40% of RNA molecules, as demonstrated by an exon-skipping assay; this splice variant is linked to the migraine-associated variant rs12355831, implicating altered mitochondrial long-chain fatty acid activation in migraine pathology. eQTL analysis of GEUVADIS RNA-seq data, exon-skipping assay with direct causality demonstration European journal of human genetics Medium 27189022
2020 A 103.3 kb deletion encompassing the ACSL5 gene (and ZDHHC6) in Australian Kelpie dogs causes complete absence of ACSL5 expression in jejunal tissue and results in intestinal lipid malabsorption, steatorrhea, and stunted growth, establishing ACSL5 as essential for intestinal long-chain fatty acid absorption in vivo. Genome-wide association analysis, whole transcriptomic sequencing confirming absent ACSL5 expression, PCR-based diagnostic test, autosomal recessive inheritance confirmation Scientific reports Medium 33106515
2024 ACSL5 regulates MHC-I-mediated antigen presentation; ACSL5 expression sensitizes tumors to PD-1 blockade and to CD8+ T cell cytotoxicity in vitro, and elaidic acid (a trans LCFA) phenocopies ACSL5 to enhance MHC-I expression and suppress tumor growth in vivo. In vivo PD-1 blockade tumor models, in vitro CD8+ T cell cytotoxicity assays, ACSL5 substrate screening, MHC-I expression assays, dietary supplementation experiments Cell metabolism High 38350448
2024 USP29 directly interacts with ACSL5 and stabilizes it by promoting K48-linked deubiquitination, thereby preventing proteasomal degradation of ACSL5; loss of USP29 reduces ACSL5 levels and fatty acid β-oxidation, exacerbating hepatic steatosis in MASLD, while the hepatoprotective effect of USP29 overexpression is dependent on ACSL5. Co-immunoprecipitation, ubiquitination assays (K48-linkage specific), USP29 KO and OE in mice and hepatocytes, rescue experiments with ACSL5 Clinical and molecular hepatology High 39355870
2024 Intestine-specific ACSL5 knockout (ACSL5IKO) mice are protected from diet-induced obesity exclusively through reduced food intake during high-fat feeding; loss of intestinal ACSL5 increases fatty acid content in the distal small intestine, elevates postprandial GLP-1 and PYY secretion, and GLP-1 receptor antagonism partially restores food intake, demonstrating that intestinal ACSL5 regulates energy balance via enteroendocrine signaling. Tamoxifen-inducible intestine-specific Cre knockout mouse model, metabolic phenotyping, GLP-1/PYY measurement after TAG challenge, GLP-1 receptor antagonist treatment, dietary fat absorption studies Molecular metabolism High 38499083
2024 STAT3 transcriptionally activates ACSL5 under high glucose/palmitic acid conditions by binding the ACSL5 promoter; ACSL5 promotes lipid deposition and lipoapoptosis in proximal tubular epithelial cells, and concurrent STAT3 knockdown with ACSL5 overexpression mitigates lipoapoptosis compared to ACSL5 overexpression alone. ChEA3 database prediction, STAT3 knockdown with RT-qPCR, promoter activation assay, ACSL5 KD and OE in BUMPT cells with Oil Red O staining, FFA ELISA, Western blot, diabetic mouse model Molecular and cellular endocrinology Medium 39557186
2025 OTUB1 directly interacts with ACSL5 (identified by mass spectrometry), deubiquitinates ACSL5, and promotes its stability; OTUB1 overexpression improves fatty acid oxidation and alleviates APAP-induced liver injury in vivo and in vitro, and this protective effect on FAO is abolished when ACSL5 is co-depleted. Mass spectrometry identification of ACSL5 as OTUB1 substrate, Co-IP, deubiquitination assay, OTUB1 OE/KD in mice and hepatocytes, ACSL5 rescue/co-depletion experiments Biochemical pharmacology High 40280245
2025 ACSL5 promotes fatty acid oxidation in colorectal cancer cells, operates within a p53 regulatory loop (p53 transcriptionally upregulates ACSL5; ACSL5 competes with MIB1 to stabilize MDM2, suppressing p53), relieves p53-mediated inhibition of PGAM1 to drive glycolysis, and its mitochondrial localization promotes IDH2 activation to accelerate the TCA cycle. ACSL5 KD/OE in colorectal cancer cells, metabolic flux assays (glycolysis, OXPHOS), Co-IP (ACSL5-MIB1-MDM2 competition), p53 transcriptional reporter assays, PGAM1 activity assay, ROS measurement, oxaliplatin sensitivity assays Advanced science Medium 41355704
2025 ACSL5 promotes cellular senescence in bladder cancer by increasing acetyl-CoA production through fatty acid oxidation; elevated acetyl-CoA drives K1360 acetylation of 53BP1, enhancing recruitment of the p53-p21 senescent signaling axis to the nucleus; DNMT1-mediated CpG methylation silences ACSL5 in bladder cancer. ACSL5 OE/KD in bladder cancer cells, acetyl-CoA measurement, 53BP1 acetylation assay (K1360 site), p53-p21 pathway analysis, DNMT1 inhibition, in vitro and in vivo senescence assays Oncogene Medium 40595416
2025 JAB1 forms a transcriptional repressor complex with CUL4B (CRL4B) that co-occupies the promoters of PPARG and ACSL5, leading to their transcriptional repression; JAB1 promotes breast cancer cell proliferation, invasion, and stemness by stabilizing CUL4B and suppressing ACSL5-mediated fatty acid metabolism. ChIP assay for CRL4B complex at PPARG/ACSL5 promoters, CUL4B stabilization assay, JAB1 OE/KD in breast cancer cells with proliferation/invasion/stemness readouts Cell death and differentiation Medium 41388188
2025 ACSL5 expression is induced in kidney tubular cells via IRF-1 signaling (part of a gamma interferon-related gene signature); ACSL5 maintains ATP production and cell viability and shapes the tubular cell lipidome by reducing ceramide accumulation and modulating glycerolipid content. Transcriptomic, metabolomic, and lipidomic analyses of experimental models and patient cohorts; IRF-1 signaling manipulation in kidney tubular cells; cell viability and ATP assays iScience Medium 40546938
2025 AURKB inhibition in rhabdomyosarcoma reduces NPM1, which decreases SP1 transcription factor activity, leading to reduced ACSL5 expression; loss of ACSL5 promotes apoptosis and ferroptosis in RMS cells, establishing an AURKB/NPM1/SP1/ACSL5 axis in apoptosis/ferroptosis resistance. AURKB inhibitor treatment, NPM1/SP1/ACSL5 KD in RMS cells, apoptosis and ferroptosis assays in vitro, xenograft tumor growth assays in vivo JCI insight Medium 39927464
2025 ACSL5 in lung-metastatic breast cancer cells facilitates adaptation to palmitic acid (PA) enriched in the pulmonary microenvironment by inducing COX2-mediated PGE2 accumulation and activating PI3K/AKT and ERK signaling through EP4; ACSL5 also boosts palmitoyltransferase levels to further enhance COX2 expression, and this axis can be blocked by the palmitoylation inhibitor 2-bromopalmitate. ACSL5 OE/KD in breast cancer cell lines, COX2/PGE2 measurement, EP4 signaling assays, palmitoyltransferase activity assays, 2-bromopalmitate inhibition, breast cancer mouse metastasis models, patient tumor analysis Cancer research Medium 41570334
2020 The ONECUT2 (OC2) transcription factor directly activates ACSL5 transcription in gastric cancer cells, as shown by ChIP-seq and RNA-seq; OC2 upregulation (driven by promoter hypomethylation) triggers ACSL5 expression in intestinal metaplasia and gastric cancer, and OC2 knockdown suppresses tumorigenesis in nude mice. ChIP-seq, RNA-seq, stable transfection/knockdown of OC2, bisulfite sequencing for methylation, xenograft tumorigenesis assay International journal of cancer Medium 32129880

Source papers

Stage 0 corpus · 55 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Recessive and dominant mutations in the ethylene biosynthetic gene ACS5 of Arabidopsis confer cytokinin insensitivity and ethylene overproduction, respectively. Proceedings of the National Academy of Sciences of the United States of America 218 9539813
1998 A novel acyl-CoA synthetase, ACS5, expressed in intestinal epithelial cells and proliferating preadipocytes. Journal of biochemistry 130 9722683
1995 ACS2, a Saccharomyces cerevisiae gene encoding acetyl-coenzyme A synthetase, essential for growth on glucose. European journal of biochemistry 100 7649171
2001 Phosphorylation of tomato 1-aminocyclopropane-1-carboxylic acid synthase, LE-ACS2, at the C-terminal region. The Journal of biological chemistry 91 11375393
2022 Cytoplasmic SIRT6-mediated ACSL5 deacetylation impedes nonalcoholic fatty liver disease by facilitating hepatic fatty acid oxidation. Molecular cell 85 36208627
2023 Hypoxia-responsive PPARGC1A/BAMBI/ACSL5 axis promotes progression and resistance to lenvatinib in hepatocellular carcinoma. Oncogene 76 36932115
2016 Acyl CoA synthetase 5 (ACSL5) ablation in mice increases energy expenditure and insulin sensitivity and delays fat absorption. Molecular metabolism 76 26977393
2021 Arabidopsis WRKY71 regulates ethylene-mediated leaf senescence by directly activating EIN2, ORE1 and ACS2 genes. The Plant journal : for cell and molecular biology 68 34296474
1999 Fusion of TEL/ETV6 to a novel ACS2 in myelodysplastic syndrome and acute myelogenous leukemia with t(5;12)(q31;p13). Genes, chromosomes & cancer 68 10502316
1996 Biochemical studies of two rat acyl-CoA synthetases, ACS1 and ACS2. European journal of biochemistry 64 8973631
2016 The type 2 diabetes presumed causal variant within TCF7L2 resides in an element that controls the expression of ACSL5. Diabetologia 61 27539148
2024 Dietary elaidic acid boosts tumoral antigen presentation and cancer immunity via ACSL5. Cell metabolism 57 38350448
2007 Transcriptional activation of hepatic ACSL3 and ACSL5 by oncostatin m reduces hypertriglyceridemia through enhanced beta-oxidation. Arteriosclerosis, thrombosis, and vascular biology 53 17761945
2020 Genome-wide Meta-analysis Finds the ACSL5-ZDHHC6 Locus Is Associated with ALS and Links Weight Loss to the Disease Genetics. Cell reports 52 33113361
2020 A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis. Communications biology 51 32968195
2007 Correlation between development of female flower buds and expression of the CS-ACS2 gene in cucumber plants. Journal of experimental botany 47 17630291
2014 Casein kinase 1 regulates ethylene synthesis by phosphorylating and promoting the turnover of ACS5. Cell reports 46 25464840
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
2017 Acquired resistance to LY2874455 in FGFR2-amplified gastric cancer through an emergence of novel FGFR2-ACSL5 fusion. Oncotarget 44 28122360
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
2019 LOX and ACSL5 as potential relapse markers for pancreatic cancer patients. Cancer biology & therapy 36 30712446
2020 ONECUT2 upregulation is associated with CpG hypomethylation at promoter-proximal DNA in gastric cancer and triggers ACSL5. International journal of cancer 29 32129880
1997 The acetyl-CoA synthetase gene ACS2 of the yeast Saccharomyces cerevisiae is coregulated with structural genes of fatty acid biosynthesis by the transcriptional activators Ino2p and Ino4p. FEBS letters 24 9326360
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 ACSL5 genotype influence on fatty acid metabolism: a cellular, tissue, and whole-body study. Metabolism: clinical and experimental 18 29605434
2011 High ACSL5 transcript levels associate with systemic lupus erythematosus and apoptosis in Jurkat T lymphocytes and peripheral blood cells. PloS one 16 22163040
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
2014 TP53 status regulates ACSL5-induced expression of mitochondrial mortalin in enterocytes and colorectal adenocarcinomas. Cell and tissue research 15 24770931
2000 Cloning of an auxin-responsive 1-aminocyclopropane-1-carboxylate synthase gene (CMe-ACS2) from melon and the expression of ACS genes in etiolated melon seedlings and melon fruits. Plant science : an international journal of experimental plant biology 14 11074269
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
2024 USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination. Clinical and molecular hepatology 12 39355870
2016 A splice variant in the ACSL5 gene relates migraine with fatty acid activation in mitochondria. European journal of human genetics : EJHG 11 27189022
2024 The transcription factor WRKY22 modulates ethylene biosynthesis and root development through transactivating the transcription of ACS5 and ACO5 in Arabidopsis. Physiologia plantarum 9 38837414
2014 Molecular cloning of the goose ACSL3 and ACSL5 coding domain sequences and their expression characteristics during goose fatty liver development. Molecular biology reports 9 24469710
2024 Intestinal Acyl-CoA synthetase 5 (ACSL5) deficiency potentiates postprandial GLP-1 & PYY secretion, reduces food intake, and protects against diet-induced obesity. Molecular metabolism 8 38499083
2024 Structural characteristics of Lacticaseibacillus rhamnosus ACS5 exopolysaccharide in association with its antioxidant and antidiabetic activity in vitro. International journal of biological macromolecules 6 39357712
2025 AURKB inhibition induces rhabdomyosarcoma apoptosis and ferroptosis through NPM1/SP1/ACSL5 axis. JCI insight 5 39927464
2024 ACSL5 promotes lipid deposition and lipoapoptosis in proximal tubular epithelial cells of diabetic kidney disease. Molecular and cellular endocrinology 5 39557186
2024 ACS2 and ACS6, especially ACS2 is involved in MPK6 evoked production of ethylene under Cd stress, which exacerbated Cd toxicity in Arabidopsis thaliana. Plant science : an international journal of experimental plant biology 5 39672386
2020 A large deletion on CFA28 omitting ACSL5 gene is associated with intestinal lipid malabsorption in the Australian Kelpie dog breed. Scientific reports 5 33106515
2018 Expression Analysis of ACSL5 and Wnt2B in Human Congenital Pulmonary Airway Malformations. The Journal of surgical research 4 30463708
2025 ACSL5 regulated acetyl-CoA to promote bladder cancer cellular senescence via 53BP1 acetylation. Oncogene 3 40595416
2022 Association of statin pretreatment with presentation characteristics, infarct size and outcome in older patients with acute coronary syndrome: the Elderly ACS-2 trial. Age and ageing 3 35716046
2025 ACS4 exerts a pivotal role in ethylene biosynthesis during the ripening of tomato fruits in comparison to ACS2. The Plant journal : for cell and molecular biology 2 40040541
2025 Scutellariae Radix and Coptidis Rhizoma improve NAFLD via regulation of SIRT6/ACSL5 pathway and SCD1. Journal of ethnopharmacology 2 40254111
2023 Regulatory roles of ACSL5 in the anti-tumor function of palmitic acid (C16:0) <em>via</em> the ERK signaling pathway. European journal of histochemistry : EJH 2 37946526
2025 OTUB1 enhances fatty acid oxidation in APAP-induced liver injury by mediating ACSL5 deubiquitination. Biochemical pharmacology 1 40280245
2025 Interferon gamma induced-ACSL5 shapes the lipidome of kidney tubular cells. iScience 1 40546938
2025 JAB1/CRL4B complex represses PPARG/ACSL5 expression to promote breast tumorigenesis. Cell death and differentiation 1 41388188
2026 ACSL5 Mediates Adaptation to the Palmitic Acid-Enriched Pulmonary Microenvironment to Enhance Metastatic Breast Cancer Cell Survival and Lung Metastasis. Cancer research 0 41570334
2026 Novel homozygous variant in ACSL5 gene causing Congenital Diarrhea and Enteropathy (CODE) with sustained therapeutic success: a case report. BMC pediatrics 0 41572200
2025 ACSL5 mediates macrophage infiltration and lipid metabolism in erythrotelangiectasia rosacea via potential pathogenic mechanisms and therapeutic targets. Scientific reports 0 40195491
2025 ACSL5 Regulates Glucose Metabolism and Chemotherapy Sensitivity in Colorectal Cancer Cells under Glutamine Deficiency. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41355704
2024 Female flowers with short ovaries in 'Lemon' cucumber (Cucumis sativus) plants and their progeny carrying the mm genotype (CS-ACS2 genes with c.97G > T mutations): a novel trimonoecious phenotype. Journal of plant research 0 39394409
1993 The nucleotide sequence of the 5' flanking region of the Arabidopsis ACS2 gene. DNA sequence : the journal of DNA sequencing and mapping 0 8219282