Affinage

ACOX1

Peroxisomal acyl-coenzyme A oxidase 1 · UniProt Q15067

Length
660 aa
Mass
74.4 kDa
Annotated
2026-06-09
57 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ACOX1 is the first and rate-limiting enzyme of peroxisomal fatty acid β-oxidation, catabolizing very-long-chain fatty acids (VLCFA, including ω-3 C24–C28 species) and generating H2O2 as a byproduct, a function essential for cellular and inter-organ metabolic homeostasis (PMID:38760332, PMID:22521832). Its peroxisomal import depends on a PTS1 signal recognized by PEX5, and the ACOX1–PEX5 translocation complex is engaged by MOXD1 to control trafficking into peroxisomes (PMID:34270617, PMID:42167911). Enzyme output is tightly tuned by post-translational regulation: SIRT5-mediated desuccinylation suppresses formation of the catalytically active dimer and lowers H2O2 and oxidative DNA damage (PMID:29491006), DUSP14-mediated dephosphorylation at Ser26 and CLIC1 binding both promote polyubiquitination and proteasomal degradation (PMID:36878899, PMID:41093222), whereas OGT-mediated O-GlcNAcylation shields ACOX1 from K48-linked ubiquitination (PMID:38547945). Transcriptionally, ACOX1 is induced by PPARα and FXR and repressed by C/EBPα and promoter methylation, with additional post-transcriptional suppression by microRNAs (PMID:40580723, PMID:38595921, PMID:33502338, PMID:38367917). The dual-edged consequence of its activity is central to disease: loss-of-function drives VLCFA accumulation, peroxisomal dysfunction, and glial/axonal degeneration, while the gain-of-function p.N237S variant stabilizes the active dimer and elevates ROS to cause oxidative-stress neurodegeneration that is reversible by antioxidants (PMID:32169171, PMID:38357503). Because ACOX1 sits at the junction of lipid catabolism and ROS production, its activity is repeatedly co-opted in cancer—supporting metabolic reprogramming in BRAF-mutant melanoma and CLL persister/tumor cells, and modulating signaling through substrate-dependent effects on β-catenin palmitoylation, PGE2 levels, and crotonyl-CoA-driven protein crotonylation (PMID:33238129, PMID:38057495, PMID:36878899, PMID:29290822, PMID:41675575).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2010 High

    Established that human ACOX1 acts through two distinct isoforms with non-redundant roles in restoring VLCFA catabolism and modulating PPARα coactivator recruitment, framing ACOX1 not only as a catabolic enzyme but as a regulator of its own transcriptional axis.

    Evidence Adenoviral ACOX1a/b rescue in Acox1-/- mice with fatty acid profiling and coactivator recruitment assay

    PMID:20195242

    Open questions at the time
    • Did not resolve structural basis for isoform substrate preference
    • Endogenous PPARα antagonism by nervonoyl-CoA not validated outside liver
  2. 2012 Medium

    Showed that reduced ACOX1 raises ROS/RNS and lipid accumulation in oligodendrocytes even without VLCFA challenge, linking ACOX1 loss directly to oxidative stress in glia.

    Evidence siRNA knockdown of Acox1 in 158N oligodendrocytes with ROS/RNS and lipid assays

    PMID:22521832

    Open questions at the time
    • Single cell line; in vivo relevance not established here
    • Source of VLCFA-independent ROS not defined
  3. 2018 High

    Resolved a key post-translational brake on ACOX1 by showing SIRT5 desuccinylation suppresses active-dimer formation, controlling H2O2 output and genome integrity.

    Evidence Co-IP, deacylase assays, SIRT5 KO mouse liver, and ACOX1-knockdown rescue with succinylation proteomics

    PMID:29491006

    Open questions at the time
    • Specific succinylated lysines governing dimerization not fully mapped
    • Physiological signals modulating peroxisomal SIRT5 unknown
  4. 2019 Medium

    Expanded ACOX1 substrate scope to PGE2 and connected it to apoptotic regulation, showing ACOX1 levels influence cell motility (via PGE2/EP1/ERK/MMP9) and p73-dependent survival.

    Evidence miR-31-5p and ACOX1 manipulation with lipidomics/PGE2 ELISA in OSCC; ACOX1 over/knockdown with caspase and p73 stability assays in lymphoma

    PMID:29290822 PMID:31401980

    Open questions at the time
    • Direct enzymatic processing of PGE2 vs. indirect effect not biochemically isolated
    • Mechanism of p73 destabilization by ACOX1 undefined
  5. 2020 High

    Distinguished two opposite disease mechanisms—loss-of-function VLCFA accumulation versus gain-of-function p.N237S ROS toxicity—establishing ACOX1 dysregulation in either direction as neurodegenerative.

    Evidence Drosophila LOF genetics, patient-derived Schwann cells expressing N237S, ROS assays, antioxidant rescue

    PMID:32169171

    Open questions at the time
    • Structural basis of N237S dimer stabilization not solved in this work
    • Human therapeutic translation of antioxidant rescue untested
  6. 2020 Medium

    Demonstrated ACOX1-driven peroxisomal FAO as a metabolic vulnerability supporting BRAF-inhibitor-tolerant melanoma persister cells, and identified a direct viral target relationship with EV71 RdRp.

    Evidence ACOX1 siRNA and thioridazine inhibition with Seahorse flux and xenografts; Co-IP of EV71 3D with ACOX1 and KD functional readouts

    PMID:32434419 PMID:33238129

    Open questions at the time
    • Selectivity of peroxisomal FAO inhibition in vivo limited by pharmacology
    • Functional consequence of 3D–ACOX1 binding for viral replication unresolved
  7. 2021 Medium

    Mapped transcriptional repression of ACOX1 by C/EBPα at defined promoter sites and post-transcriptional repression by miR-25-3p, linking ACOX1 dosage to adipogenesis.

    Evidence EMSA, ChIP, promoter mutagenesis, luciferase, and miR-25-3p assays in bovine preadipocytes

    PMID:33502338

    Open questions at the time
    • Bovine ortholog; conservation of these elements in human promoter untested
    • Interplay with PPARα activation not addressed
  8. 2021 Medium

    Validated the conserved PTS1/PEX5 import requirement for ACOX1 and its developmental necessity using a nematode ortholog.

    Evidence In vitro/in vivo FAO assays, ACOX-1/PEX-5 Co-IP, PTS1 mutagenesis, RNAi developmental phenotyping in H. contortus

    PMID:34270617

    Open questions at the time
    • Demonstrated in nematode ortholog; human import kinetics not measured
    • Regulatory inputs to import not addressed
  9. 2022 Medium

    Defined PPARα as a selective inducer of ACOX1 (distinct from catalase) and placed ACOX1 downstream of a PLA2/COX-2 axis metabolizing arachidonic acid/PGE2.

    Evidence PPARα agonist/withdrawal and PEX16/Pparα double-KO mice; pharmacological PLA2/COX-2/ACOX1 inhibition with TG and PGE2 measurement

    PMID:35526488 PMID:40580723

    Open questions at the time
    • Direct PPARα binding to ACOX1 promoter not shown in these studies
    • Quantitative contribution of ACOX1 to PGE2 turnover in vivo uncertain
  10. 2023 High

    Uncovered a feedforward oncogenic circuit in which DUSP14 dephosphorylates ACOX1 (Ser26) to drive its degradation, and substrate palmitic acid palmitoylates β-catenin to activate Wnt signaling, with β-catenin/c-Myc reinforcing ACOX1 suppression.

    Evidence In vitro dephosphorylation, Co-IP, ubiquitination and palmitoylation assays, S26 mutagenesis, xenografts and CRC clinical samples

    PMID:36878899

    Open questions at the time
    • Kinase counteracting DUSP14 on Ser26 not identified
    • Generality of the loop beyond colorectal cancer untested
  11. 2023 Medium

    Connected epigenetic silencing of ACOX1 to organ fibrosis and identified ACOX1 as a metabolic dependency in CLL B cells.

    Evidence TLR4/NF-κB/DNMT1 promoter-methylation manipulation in renal transplant model; ACOX1 KD/inhibition with Seahorse and cell-death assays in patient CLL cells

    PMID:38057495 PMID:38367917

    Open questions at the time
    • Direct DNMT1 occupancy at ACOX1 promoter inferred, not fully mapped
    • Mechanism of metabolic switch upon ACOX1 loss in CLL incompletely defined
  12. 2024 High

    Established ACOX1 as a hub of an inter-organ axis and a target of stabilizing/destabilizing PTMs and nuclear receptors, linking hepatic ACOX1 output to adipose browning via GPR120 and to FXR/OGT regulation.

    Evidence Liver-specific Acox1 KO with lipidomics and GPR120 signaling; OGT KO and O-GlcNAcylation/ubiquitination assays; FXR silencing/agonism in hepatocytes and FXR-/- mice

    PMID:38547945 PMID:38595921 PMID:38760332

    Open questions at the time
    • O-GlcNAcylation site on ACOX1 not pinpointed
    • Direct vs. indirect FXR regulation of ACOX1 unresolved
  13. 2025 Medium

    Defined MOXD1 as a trafficking regulator of the ACOX1–PEX5 complex and a druggable node for metabolic liver disease, while extending ACOX1's reach to substrate-driven membrane signaling and crotonylation-based redox control.

    Evidence Co-IP-MS, interface-residue mapping, genetic mouse models and rM15 pharmacology (MASH); lipidomics/membrane fractionation for cerebroside–MET/IGF1R effects; HIF-1α-driven ACOX1, crotonyl-CoA, HSP90AB1 K265 crotonylation, MD simulation and TXN stabilization; DDX1/HNRNPK-mediated ACOX1 alternative splicing; CLIC1-driven ACOX1 degradation

    PMID:39885295 PMID:41093222 PMID:41197750 PMID:41675575 PMID:42167911

    Open questions at the time
    • Structural model of MOXD1–ACOX1–PEX5 interface based on modelling not experimental structure
    • Several mechanisms (CLIC1, DDX1 splicing) rest on single-lab data
    • Direct enzymatic flux producing crotonyl-CoA from ACOX1 not quantified in cells
  14. 2025 Medium

    Demonstrated that peroxisomal FAO via ACOX1 is required for retinal metabolic homeostasis and that ACOX1 overexpression drives ROS→mTOR inhibition→autophagy to restrain colorectal cancer growth.

    Evidence Global Acox1 KO mice with multi-omics and dietary rescue; ACOX1 overexpression with MS FAO profiling, mTOR/autophagy readouts and xenografts

    PMID:39849090 PMID:40049514

    Open questions at the time
    • Tissue-specific contribution of ACOX1 in retina vs. systemic effects not separated
    • Threshold of ROS distinguishing tumor-suppressive vs. tumor-supportive ACOX1 outcomes undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the opposing context-dependent outcomes of ACOX1 activity—tumor-suppressive ROS/autophagy versus pro-survival metabolic and redox support—are determined within a single cell remains unresolved.
  • No unified model reconciling tumor-suppressive and tumor-supportive roles
  • Quantitative thresholds linking ACOX1-derived H2O2 to distinct downstream pathways unknown
  • Structural determinants of the active dimer and its regulation by PTMs not solved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 4 GO:0140098 catalytic activity, acting on RNA 4
Localization
GO:0005777 peroxisome 5
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-8953897 Cellular responses to stimuli 4
Partners
CLIC1DUSP14MOXD1OGTPEX5SIRT5

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 SIRT5-mediated desuccinylation inhibits ACOX1 enzymatic activity by suppressing its active dimer formation. SIRT5 is present in peroxisomes and ACOX1 is a physiological substrate of SIRT5; deletion of SIRT5 increases ACOX1 succinylation and activity, leading to elevated H2O2 production and oxidative DNA damage that is rescued by ACOX1 knockdown. Co-IP, deacylase activity assay, SIRT5 knockout mouse livers, ACOX1 knockdown rescue experiments, succinylation proteomics EMBO reports High 29491006
2020 Loss-of-function mutations in ACOX1 cause glial and axonal loss via accumulation of very-long-chain fatty acids and peroxisomal dysfunction, whereas a gain-of-function variant (p.N237S) causes increased ACOX1 protein levels and elevated reactive oxygen species in glia (Schwann cells/oligodendrocytes), leading to neurodegeneration via a distinct oxidative-stress mechanism. Antioxidant treatment suppressed p.N237S-induced neurodegeneration in flies and primary Schwann cells. Drosophila ACOX1 loss-of-function genetics, patient-derived murine Schwann cells expressing N237S variant, ROS assays, antioxidant rescue experiments Neuron High 32169171
2023 DUSP14 phosphatase dephosphorylates ACOX1 at serine 26, promoting its polyubiquitination and proteasomal degradation. Loss of ACOX1 leads to accumulation of its substrate palmitic acid (PA), which palmitoylates β-catenin at cysteine 466, blocking CK1/GSK3-directed phosphorylation and β-TrCP-mediated degradation of β-catenin, thereby stabilizing β-catenin and activating Wnt signaling to promote colorectal cancer progression. Stabilized β-catenin in turn transcriptionally represses ACOX1 and activates DUSP14 via c-Myc, forming a feedforward loop. In vitro dephosphorylation assay, co-IP, ubiquitination assay, site-directed mutagenesis (S26), palmitoylation assay, mouse xenograft models, patient-derived xenograft experiments, CRC clinical samples Cell discovery High 36878899
2010 Human ACOX1 has two isoforms (ACOX1a and ACOX1b) from a single gene; ACOX1b is markedly more effective than ACOX1a in reversing the Acox1-null hepatic phenotype in mice. ACOX1b expression restores nervonic acid production, which negatively impacts recruitment of coactivators to the PPARα-response unit (suggesting nervonic acid/nervonoyl-CoA as endogenous PPARα antagonist). Restoration of DHA requires concomitant expression of both isoforms. Adenoviral ACOX1a/b expression in Acox1-/- mice, fatty acid profiling, PPARα coactivator recruitment assay, liver phenotype analysis Laboratory investigation High 20195242
2024 Hepatic ACOX1-mediated peroxisomal β-oxidation catabolizes very-long-chain fatty acids (VLCFA, C24–C28 ω-3 species); liver-specific Acox1 knockout increases circulating ω-3 VLCFAs that promote adipose browning, mitochondrial biogenesis, and Glut4 translocation through activation of the lipid sensor GPR120 in adipocytes, establishing an inter-organ communication axis regulating metabolic homeostasis. Liver-specific Acox1 knockout mice, serum lipidomics, white adipocyte browning assay, GPR120 signaling assay, conditioned serum experiments on cultured adipocytes Nature communications High 38760332
2020 ACOX1 is the key peroxisomal fatty acid β-oxidation enzyme supporting metabolic reprogramming from glycolysis to oxidative respiration in BRAF(V600E) melanoma persister cells tolerant to BRAF/MEK inhibitors. Knockdown of ACOX1 or treatment with the peroxisomal FAO inhibitor thioridazine specifically suppresses oxidative respiration of persister cells and decreases their emergence. PPARα transcriptionally regulates this FAO program. ACOX1 siRNA knockdown, thioridazine pharmacological inhibition, Seahorse metabolic flux assay, mouse xenograft experiments Cell reports High 33238129
2024 O-GlcNAcylation by OGT (O-GlcNAc transferase) protects ACOX1 from ubiquitination-dependent proteasomal degradation. The OGT-ACOX1 interaction at the K48 site precludes K48-linked ubiquitination; deletion of O-GlcNAcylation disrupts lipid metabolism with accumulation of medium- and long-chain fatty acids. Co-immunoprecipitation, ubiquitination assay, OGT knockout mice, in vitro lipid metabolism analysis, AML-12 cell OGT inhibitor treatment International journal of biological macromolecules Medium 38547945
2019 ACOX1 processes prostaglandin E2 (PGE2) as a substrate; the miR-31-5p–ACOX1 axis controls extracellular PGE2 levels in OSCC cells, modulating cell migration and invasion through EP1–ERK–MMP9 signaling. miR-31-5p directly suppresses ACOX1 expression, leading to PGE2 accumulation and enhanced cell motility. miR-31-5p overexpression/knockdown, ACOX1 knockdown, lipidomics, PGE2 ELISA, migration/invasion assays, EP1/ERK/MMP9 pathway analysis Theranostics Medium 29290822
2019 ACOX1 overexpression in lymphoma cells destabilizes p73 protein (but not p53), reducing p73 expression. Downregulation of ACOX1 promotes mitochondrial translocation of Bad, reduces mitochondrial membrane potential, and activates caspase-9 and caspase-3-dependent apoptosis. p73 expression is required for the apoptotic induction seen upon ACOX1 knockdown. ACOX1 overexpression/knockdown, caspase activity assay, mitochondrial membrane potential assay, mitochondrial fractionation (Bad localization), p73 stability assay BMB reports Medium 31401980
2020 EV71 non-structural protein 3D (RdRp) directly interacts with ACOX1 protein and promotes ACOX1 downregulation. ACOX1 knockdown alone induces apoptosis and autophagy in neural cells, reduces peroxisome numbers, increases ROS, and attenuates the DJ-1/NRF2/HO-1 cytoprotective pathway. Co-IP (3D–ACOX1 interaction), ACOX1 siRNA knockdown, peroxisome counting, ROS assay, apoptosis/autophagy assays, NRF2/HO-1 pathway analysis Virulence Medium 32434419
2021 In Haemonchus contortus (parasitic nematode), ACOX1 proteins show fatty acid oxidation activity in vitro and in vivo and interact with the peroxisomal targeting receptor PEX-5 via a peroxisomal targeting signal type 1 (PTS1) sequence. PTS1 is required for ACOX-1 recognition by PEX-5. Knockdown of acox-1 impairs post-embryonic larval development. In vitro and in vivo fatty acid oxidation assay, co-IP (ACOX-1/PEX-5), PTS1 mutagenesis, RNAi knockdown, developmental phenotyping PLoS pathogens Medium 34270617
2022 PPARα transcriptionally regulates ACOX1 mRNA and protein expression (but not catalase). PPARα agonist WY-14,643 induces ACOX1 to a greater extent than catalase; after agonist withdrawal, ACOX1 returns to baseline faster. In liver-specific PEX16 knockout (peroxisome-absent) mice crossed with Pparα-/- mice, upregulated ACOX1 protein is suppressed by PPARα ablation, while catalase remains elevated. PPARα agonist/withdrawal experiments, liver-specific PEX16 KO and Pparα-/- double-KO mice, mRNA and protein quantification Biochemical and biophysical research communications Medium 40580723
2022 PPARα agonist WY-14,643 induces a PLA2/COX-2/ACOX1 pathway in which arachidonic acid (AA) released by PLA2 from phospholipids is metabolized by ACOX1 (oxidizing PGE2). ACOX1-specific inhibitor restores both WY-14,643-suppressed liver TG and PGE2 levels, establishing that ACOX1 oxidizes PGE2/AA as substrates downstream of the PLA2/COX-2 axis in peroxisomal FAO. PPARα agonist treatment in mice (liquid diet), ACOX1-specific inhibitor (10,12-tricosadiynoic acid), COX-2 inhibitor, liver TG and PGE2 measurement Biochemical and biophysical research communications Medium 35526488
2023 ACOX1 downregulation in renal allografts is induced by TLR4–NF-κB signaling via DNA methyltransferase 1 (DNMT1)-dependent promoter methylation. ACOX1 deficiency leads to lipid accumulation and excessive oxidation of polyunsaturated fatty acids (PUFAs), promoting epithelial-mesenchymal transition (EMT) and extracellular matrix reorganization via endoplasmic reticulum (ER) stress, causing fibrosis. TLR4/NF-κB pathway manipulation, DNMT1 inhibition, ACOX1 KD/KO in renal cells, ER stress assay, EMT/ECM markers, rat renal transplant model Pharmacological research Medium 38367917
2025 MOXD1 directly interacts with the ACOX1–PEX5 translocation complex, promoting ACOX1 trafficking to peroxisomes and blocking lipolysis/lipophagy. Four key MOXD1 residues required for ACOX1 binding were identified. A small molecule (rM15) that directly binds MOXD1 and blocks its interaction with ACOX1 reduces hepatocyte lipid accumulation and suppresses diet-induced MASH in vivo. Co-IP mass spectrometry, structural modelling, colocalization analysis, hepatocyte-specific transgenic/KO mice, AAV8 knockdown model, small molecule screening and in vitro/in vivo pharmacology Gut High 42167911
2025 CLIC1 protein binds ACOX1 protein, reduces ACOX1 stability, and facilitates its polyubiquitination-dependent proteasomal degradation, thereby decreasing ACOX1 levels and enhancing cellular oxidative stress to promote gastric cancer progression. Co-IP (CLIC1–ACOX1), ubiquitination assay, ACOX1 knockdown/overexpression, oxidative stress assay, gastric cancer cell proliferation/migration assays International journal of biological macromolecules Medium 41093222
2025 Glucose starvation induces crotonylation of DDX1 (DEAD-box helicase 1) at lysine 490 (regulated by crotonyltransferase GCN5 and decrotonylase HDAC1), enhancing DDX1 interaction with HNRNPK, which mediates mutually exclusive alternative splicing of ACOX1. The resulting ACOX1 splice variant promotes peroxisomal ROS generation, enhancing oxidative damage and suppressing colorectal cancer cell proliferation. Crotonylation site mapping, DDX1 K490 mutagenesis, HNRNPK co-IP, ACOX1 alternative splicing analysis (RT-PCR/RNA-seq), ROS assay, CRC cell proliferation assay Free radical biology & medicine Medium 41197750
2025 Hypoxia induces HIF-1α-dependent transcriptional upregulation of ACOX1, which increases crotonyl-CoA levels driving site-specific crotonylation of HSP90AB1 at lysine 265. K265 crotonylation induces conformational compaction of HSP90AB1, strengthening its interaction with thioredoxin (TXN) and enhancing TXN stability to buffer ROS. Pharmacological inhibition of ACOX1 (10,12-tricosadiynoic acid) or K265R mutagenesis disrupts this axis and synergizes with cisplatin to suppress tumor growth. HIF-1α manipulation, ACOX1 inhibitor treatment, HSP90AB1 K265 mutagenesis, crotonylation proteomics, molecular dynamics simulation, co-IP (HSP90AB1–TXN), in vivo tumor xenograft Research (Washington, D.C.) Medium 41675575
2025 Inhibition of ACOX1 promotes accumulation of VLCFA-containing cerebrosides, which alter MET and IGF1R interaction with the plasma membrane and selectively inhibit their association with plasma membrane signaling platforms, reducing MET and IGF1R kinase activity in multiple myeloma cells without disrupting membrane platform integrity. Genetic and pharmacological ACOX1 inhibition, lipidomics (cerebroside accumulation), MET/IGF1R membrane fractionation, kinase activity assays, bortezomib-resistant MM xenograft model Leukemia Medium 39885295
2024 FXR (farnesoid X receptor) regulates ACOX1 expression: FXR silencing decreases ACOX1 mRNA and protein, while FXR activation with GW4064 increases ACOX1 expression in hepatocytes. Activated ACOX1 correlates with elevated serum LDL, triglycerides, and aggravated hepatic steatosis in FXR-/- mice. FXR shRNA knockdown, FXR agonist (GW4064) treatment, ACOX1 expression measurement in FXR-/- mice and hepatocyte cell lines Frontiers in pharmacology Medium 38595921
2025 In Acox1 knockout mice, retinal dysfunction is accompanied by reduced mitochondrial number and mitochondrial DNA copy number, decreased retinal pyruvate, and a decrease in ω-3 fatty acids with compensatory increase in ω-6 fatty acids. Nutrient supplementation with pyruvate, DHA (n-3), or DHA plus arachidonic acid (n-6) mitigated retinal dysfunction progression, establishing peroxisomal FAO as essential for retinal metabolic homeostasis. Global Acox1 KO mice, retinal electrophysiology, proteomics, metabolomics, fatty acid profiling, nutrient supplementation (pyruvate, DHA, AA) Journal of advanced research Medium 40049514
2012 siRNA knockdown of ACOX1 in murine oligodendrocytes increases ROS and RNS production even in the absence of VLCFA, and potentiates VLCFA-induced ROS overproduction. Reduced Acox1 levels strongly enhance VLCFA and neutral lipid accumulation in oligodendrocytes both with and without exogenous VLCFA treatment. siRNA knockdown of Acox1 in 158N oligodendrocytes, ROS/RNS assay, lipid accumulation measurement, SOD/catalase activity assay Neuroscience Medium 22521832
2023 ACOX1 is overexpressed in CLL B-lymphocytes and its downmodulation is sufficient to shift CLL cell metabolism from lipid-based to carbon/amino-acid-based oxidative phosphorylation. Complete ACOX1 blockade causes lipid droplet accumulation and caspase-dependent cell death. ACOX1 inhibition combined with BTK inhibitors has a synergistic killing effect on CLL cells. ACOX1 knockdown, pharmacological ACOX1 inhibition, Seahorse metabolic flux assay, carnitine metabolite profiling, caspase assay, lipid droplet staining, patient CLL samples Leukemia Medium 38057495
2021 C/EBPα transcription factor directly binds the bovine ACOX1 promoter at three sites (-1142 to -1129 bp, -831 to -826 bp, -303 to -298 bp) and inhibits ACOX1 transcription. miR-25-3p directly targets the ACOX1 3'UTR to suppress ACOX1 expression post-transcriptionally. ACOX1 positively regulates bovine intramuscular preadipocyte adipogenesis. Promoter deletion analysis, site-directed mutagenesis, EMSA, ChIP, dual-luciferase assay, miR-25-3p overexpression, gain/loss-of-function adipogenesis assays Journal of molecular endocrinology Medium 33502338
2024 ACOX1 gain-of-function variant p.N237S stabilizes the active ACOX1 dimer (as confirmed in zebrafish model), resulting in dysregulated enzymatic activity, increased oxidative stress, activation of the integrated stress response (ISR), and reduced peroxisome density, leading to motor impairment. The reactive microglia-targeted antioxidant dendrimer-N-acetyl-cysteine conjugate restored swimming ability in mutant zebrafish. Zebrafish transient overexpression of human ACOX1-N237S-GFP, SKL-targeted mCherry peroxisome reporter, ISR assay, oligodendrocyte counting, antioxidant (dendrimer-NAC) rescue Frontiers in pediatrics Medium 38357503
2026 ACOX1 overexpression increases ROS derived from fatty acid β-oxidation (as shown by mass spectrometry revealing increased FAO), reduces mTOR phosphorylation/activation, and enhances autophagy to suppress colorectal cancer cell proliferation and migration. The pathway was established as ROS→mTOR inhibition→autophagy induction. ACOX1 overexpression in CRC cells, mass spectrometry (FAO profiling), ROS assay, mTOR phosphorylation (Western blot), autophagy assay, in vivo xenograft Scientific reports Medium 39849090

Source papers

Stage 0 corpus · 57 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 SIRT5 inhibits peroxisomal ACOX1 to prevent oxidative damage and is downregulated in liver cancer. EMBO reports 247 29491006
2023 PPARα/ACOX1 as a novel target for hepatic lipid metabolism disorders induced by per- and polyfluoroalkyl substances: An integrated approach. Environment international 143 37572494
2020 Melanoma Persister Cells Are Tolerant to BRAF/MEK Inhibitors via ACOX1-Mediated Fatty Acid Oxidation. Cell reports 133 33238129
2020 Loss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via Different Mechanisms. Neuron 110 32169171
2012 Evidence of oxidative stress in very long chain fatty acid--treated oligodendrocytes and potentialization of ROS production using RNA interference-directed knockdown of ABCD1 and ACOX1 peroxisomal proteins. Neuroscience 99 22521832
2018 MiR-31-5p-ACOX1 Axis Enhances Tumorigenic Fitness in Oral Squamous Cell Carcinoma Via the Promigratory Prostaglandin E2. Theranostics 86 29290822
2023 Reprogramming of palmitic acid induced by dephosphorylation of ACOX1 promotes β-catenin palmitoylation to drive colorectal cancer progression. Cell discovery 79 36878899
2010 Reversal of mouse Acyl-CoA oxidase 1 (ACOX1) null phenotype by human ACOX1b isoform [corrected]. Laboratory investigation; a journal of technical methods and pathology 74 20195242
2020 Enterovirus 71 induces neural cell apoptosis and autophagy through promoting ACOX1 downregulation and ROS generation. Virulence 69 32434419
2024 Liver ACOX1 regulates levels of circulating lipids that promote metabolic health through adipose remodeling. Nature communications 60 38760332
2019 MicroRNA-15a Regulates the Differentiation of Intramuscular Preadipocytes by Targeting ACAA1, ACOX1 and SCP2 in Chickens. International journal of molecular sciences 39 31434294
2019 miR-222 targets ACOX1, promotes triglyceride accumulation in hepatocytes. Hepatobiliary & pancreatic diseases international : HBPD INT 33 31126802
2022 PPARα agonist WY-14,643 induces the PLA2/COX-2/ACOX1 pathway to enhance peroxisomal lipid metabolism and ameliorate alcoholic fatty liver in mice. Biochemical and biophysical research communications 26 35526488
2023 Shenge Formula attenuates high-fat diet-induced obesity and fatty liver via inhibiting ACOX1. Phytomedicine : international journal of phytotherapy and phytopharmacology 23 37992491
2023 ACOX1-mediated peroxisomal fatty acid oxidation contributes to metabolic reprogramming and survival in chronic lymphocytic leukemia. Leukemia 23 38057495
2021 ACOX1, regulated by C/EBPα and miR-25-3p, promotes bovine preadipocyte adipogenesis. Journal of molecular endocrinology 21 33502338
2022 MiR-103-3p promotes hepatic steatosis to aggravate nonalcoholic fatty liver disease by targeting of ACOX1. Molecular biology reports 18 35606603
2007 Association of the polymorphism in GYS1 and ACOX1 genes with meat quality traits in pigs. Animal : an international journal of animal bioscience 17 22444879
2020 Lipid Metabolism and Axon Degeneration: An ACOX1 Balancing Act. Neuron 15 32437651
2019 ACOX1 destabilizes p73 to suppress intrinsic apoptosis pathway and regulates sensitivity to doxorubicin in lymphoma cells. BMB reports 15 31401980
2024 ACOX1 deficiency-induced lipid metabolic disorder facilitates chronic interstitial fibrosis development in renal allografts. Pharmacological research 14 38367917
2024 O-GlcNAcylation regulates long-chain fatty acid metabolism by inhibiting ACOX1 ubiquitination-dependent degradation. International journal of biological macromolecules 12 38547945
2023 Two Argan Oil Phytosterols, Schottenol and Spinasterol, Attenuate Oxidative Stress and Restore LPS-Dysregulated Peroxisomal Functions in Acox1 and Wild-Type BV-2 Microglial Cells. Antioxidants (Basel, Switzerland) 12 36671029
2023 SLC9A5 promotes tumor growth and cell motility via ACOX1-mediated peroxisomal fatty acid oxidation. Experimental cell research 11 37380010
2022 Role of acyl-coenzyme A oxidase 1 (ACOX1) on palmitate-induced inflammation and ROS production of macrophages in large yellow croaker (Larimichthys crocea). Developmental and comparative immunology 11 35961593
2025 ACOX1 activates autophagy via the ROS/mTOR pathway to suppress proliferation and migration of colorectal cancer. Scientific reports 10 39849090
2020 Novel ACOX1 mutations in two siblings with peroxisomal acyl-CoA oxidase deficiency. Brain & development 10 33234382
2022 Child Neurology: Neurodegenerative Encephalomyelopathy Associated With ACOX1 Gain-of-Function Variation Partially Responsive to Immunotherapy. Neurology 9 35715200
2021 Lipid metabolism disorders effects of 6:2 chlorinated polyfluorinated ether sulfonate through Hsa-miRNA-532-3p/Acyl-CoA oxidase 1(ACOX1) pathway. Ecotoxicology and environmental safety 9 34837870
2011 Molecular characterization, polymorphism of the ACOX1 gene and association with ultrasound traits in Bos taurus. Genetics and molecular research : GMR 9 21948757
2023 A de novo heterozygous variant in ACOX1 gene cause Mitchell syndrome: the first case in China and literature review. BMC medical genomics 8 37400800
2025 PPARα regulates acyl-CoA oxidase 1 (ACOX1) but not catalase. Biochemical and biophysical research communications 7 40580723
2021 Acyl-CoA oxidase ACOX-1 interacts with a peroxin PEX-5 to play roles in larval development of Haemonchus contortus. PLoS pathogens 7 34270617
2019 The Associations of PMF1, ICAM1, AGT, TRIM65, FBF1, and ACOX1 Variants With Leukoaraiosis in Chinese Population. Frontiers in genetics 7 31396257
2016 Early white matter involvement in an infant carrying a novel mutation in ACOX1. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 7 26965209
2024 Inhibition of ACOX1 enhances the therapeutic efficacy of obeticholic acid in treating non-alcoholic fatty liver disease and mitigates its lipotoxicity. Frontiers in pharmacology 6 38595921
2020 Variation in the SLC16A1 and the ACOX1 Genes Is Associated with Gallop Racing Performance in Arabian Horses. Journal of equine veterinary science 6 32972674
2020 Variability of ACOX1 Gene Polymorphisms across Different Horse Breeds with Regard to Selection Pressure. Animals : an open access journal from MDPI 5 33260884
2025 Targeting ABCD1-ACOX1-MET/IGF1R axis suppresses multiple myeloma. Leukemia 4 39885295
2025 Nutrient supplementation mitigates retinal dysfunction in Acox1 knockout mice with impaired peroxisomal fatty acid oxidation. Journal of advanced research 4 40049514
2025 Ferulic acid attenuates Sarcopenia progression by inhibiting peroxisomal ACOX1. Free radical biology & medicine 4 40816648
2024 Generation and characterization of a zebrafish gain-of-function ACOX1 Mitchell disease model. Frontiers in pediatrics 3 38357503
2025 Breviscapine regulates lipid metabolism of microglia via the ADORA1/PPARα/ACOX1 pathway to promote spinal cord injury recovery. International immunopharmacology 2 40628044
2024 Dermatopathological features and successful treatment with topical antioxidant for ichthyosiform lesions in Mitchell syndrome caused by an ACOX1 variant. The Journal of dermatology 2 38923010
2024 ACOX1 gain-of-function variation in a 10-years-old patient responsive to immunomodulating therapy. American journal of medical genetics. Part A 2 38923841
2024 Tumor-derived exosomal miR-103a-3p promotes vascular permeability and proliferation by targeting ZO-1 and ACOX-1 in nasopharyngeal carcinoma. Translational cancer research 2 39430846
2023 Loss of ACOX1 in clear cell renal cell carcinoma and its correlation with clinical features. Open life sciences 2 37724116
2025 Primary adrenal insufficiency caused by pseudo-neonatal adrenoleukodystrophy associated with biallelic ACOX1 mutations. European journal of endocrinology 1 40326779
2025 FNDC5 and ACOX1 as Biomarkers of Peroxisomal Activity with Contrast Outcomes in Colon Adenocarcinoma. Biological procedures online 1 40702462
2025 DDX1 crotonylation mediates ACOX1 alternative splicing through HNRNPK to increase peroxisomal oxidative damage. Free radical biology & medicine 1 41197750
2026 Hypoxic Reprogramming of ACOX1-Driven HSP90AB1 Crotonylation Stabilizes Thioredoxin to Orchestrate Redox Homeostasis in Oral Squamous Cell Carcinoma. Research (Washington, D.C.) 0 41675575
2026 Annexin A1 exacerbates islet stellate cell activation by regulating triglyceride catabolism via the PPARα/ACOX1/CYP4a pathway. Islets 0 41723748
2026 Enhanced oxidative stress resilience in C. elegans acox-1.1 mutants through CTL-3 and proteasomal regulation. Experimental biology and medicine (Maywood, N.J.) 0 41908884
2026 Blocking MOXD1-derived ACOX1 peroxisome trafficking suppresses metabolic dysfunction-associated steatohepatitis. Gut 0 42167911
2025 Extract of camellia seed cake ameliorates glycolipid metabolism disorder in mice through inhibiting ACOX1 activity. Food chemistry: X 0 40686867
2025 CLIC1 regulates cellular oxidative stress and gastric cancer progress by enhancing ACOX1 ubiquitination. International journal of biological macromolecules 0 41093222
2024 Study of Variation of ACOX1 Gene Among Different Horse Breeds Maintained in Iran. Animals : an open access journal from MDPI 0 39765470

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