ArticleThe EMBO journal2025
SLC25A1 and ACLY maintain cytosolic acetyl-CoA and regulate ferroptosis susceptibility via FSP1 acetylation.
Article in The EMBO journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- ZFP36-ferroptosis axis as a key renal protective pathway in diabetic kidney disease.Endocrine journal · 2026Article
- Targeting non-coding RNAs in the ferroptosis system: Molecular mechanisms and clinical translation for reversing doxorubicin resistance in breast cancer.Non-coding RNA research · 2026Review
- ACLY alleviates cerebral ischemia/reperfusion injury by reducing oxidative stress and enhancing mitochondrial function via histone acetylation.Cell death & disease · 2026Article
- P4HA3 drives cervical cancer lymphatic metastasis by facilitating ACLY-mediated ferroptosis resistance.Cell death and differentiation · 2026Article
- Vacuolar iron transporters mediate resistance to triadimefon in plant pathogenic fungi.Nature communications · 2026Article
- ETV4 promotes colorectal cancer progression through SLC7A11-mediated ferroptosis inhibition.Biology direct · 2026Article
- SLC25A1 upregulation promotes HNSCC cisplatin resistance via H3K27ac-mediated cellular senescence.NPJ precision oncology · 2026Article
- Lidocaine inhibits hepatocellular carcinoma cell proliferation, migration, and invasion through the downregulation of SLC6A3.Scientific reports · 2026Article
- A Modular Platform for Effector Discovery in Induced-Proximity Lysine Acetylation.bioRxiv : the preprint server for biology · 2026Article
- METTL16 antagonizes astaxanthin-induced ferroptosis in colorectal cancer cells.Translational cancer research · 2026Article
- Solasonine inhibits NSCLC malignant progression by regulating SLC7A11 ubiquitination degradation and inducing ferroptosis.Respiratory research · 2026Article
- Ferroptosis in cancer toward molecular insights and clinical translation in pancreatic cancer.Molecular cancer · 2026Review
- Regulation of apoptosis, ferroptosis, and pyroptosis mediated by acetylation.Cell death discovery · 2026Review
- Membrane Stress and Ferroptosis: Lipid Dynamics in Cancer.International journal of molecular sciences · 2026Review
- The regulatory roles and therapeutic strategies of the solute carrier transporters in cancer metabolism.NPJ precision oncology · 2026Review
- Long Non-Coding RNA PVT1 Promotes Doxorubicin Resistance by Inhibiting Ferroptosis in Breast Cancer.Breast cancer (Dove Medical Press) · 2026Article
- ACSL4-Mediated Ferroptosis and its Biological Functions and Potential Therapeutic Significance in Liver Diseases.Current pharmaceutical design · 2026Review
- Protein Post-Translational Modifications in the Regulation of Ferroptosis: New Opportunities and Challenges for Cancer Immunotherapy.International journal of biological sciences · 2026Review
- Post-translational modifications in ferroptosis: mechanisms and therapeutic potential.International journal of biological sciences · 2026Review
- ACSS1 co-opts acetyl-CoA metabolism to drive DNA repair and undermine radiotherapy efficacy in breast cancer.Cell death & disease · 2025Article
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Authors and funding
12 authors.
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Abstract
Ferroptosis, an iron-dependent form of programmed cell death characterized by excessive lipid hydroperoxides accumulation, emerges as a promising target in cancer therapy. Among the solute carrier (SLC) superfamily, the cystine/glutamate transporter system antiporter components SLC3A2 and SLC7A11 are known to regulate ferroptosis by facilitating cystine import for ferroptosis inhibition. However, the contribution of additional SLC superfamily members to ferroptosis remains poorly understood. Here, we use a targeted CRISPR-Cas9 screen of the SLC superfamily to identify SLC25A1 as a critical ferroptosis regulator in human cancer cells. SLC25A1 drives citrate export from the mitochondria to the cytosol, where it fuels acetyl-CoA synthesis by ATP citrate lyase (ACLY). This acetyl-CoA supply sustains FSP1 acetylation and prevents its degradation by the proteasome via K29-linked ubiquitin chains. K168 is the primary site of FSP1 acetylation and deacetylation by KAT2B and HDAC3, respectively. Pharmacological inhibition of SLC25A1 and ACLY significantly enhances cancer cell susceptibility to ferroptosis both in vitro and in vivo. Targeting the SLC25A1-ACLY axis is therefore a potential therapeutic strategy for ferroptosis-targeted cancer intervention.
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