ArticleNature communications2022
The lipid flippase SLC47A1 blocks metabolic vulnerability to ferroptosis.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 129 citations in OpenAlex.
- Distinct mechanism of syntaxin3-dependent tight junction assembly in keratinocyte model cells.Cell and tissue research · 2026Article
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Epigenetic Regulation of Ferroptosis in Inflammation: Molecular Mechanisms and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Ferroptosis as a target mechanism in heart and kidney disease.The Journal of clinical investigation · 2026Review
- Dual targeting of ferroptosis and immune evasion: STAT3 inhibition as a one-two punch for breast cancer immunotherapy.Journal of translational internal medicine · 2026Article
- The two faces of JAK-STAT.eLife · 2026Article
- Regulated cell death plasticity in cancer: thresholds, reversibility, and therapeutic failure.Journal of translational medicine · 2026Review
- Metal-dependent regulated cell death: Molecular architecture and translational frontiers.iMeta · 2026Review
- Translating ferroptosis into oncology: challenges, opportunities and future directions.Nature reviews. Clinical oncology · 2026Review
- Inhibition of NCOA4-mediated ferritinophagy improves cardiac remodeling in diabetic cardiomyopathy via MITOL/parkin signaling.Molecular and cellular biochemistry · 2026Article
- Targeting ferroptosis in cancer: from mechanistic insights to therapeutic approaches.Molecular biomedicine · 2026Review
- PDHA1 enhances resistance to ferroptosis in anoikis-resistant prostate cancer by upregulating AIFM2.Cell death discovery · 2026Article
- PPARa-FSP1 axis modulates lipid peroxidation-induced neuronal ferroptosis to promote functional recovery in mouse model of traumatic spinal cord injury.Cellular and molecular life sciences : CMLS · 2026Article
- Targeting C12ORF49-Mediated Ferroptosis in Hepatocellular Carcinoma.JGH open : an open access journal of gastroenterology and hepatology · 2026Review
- Photothermal therapy triggering organelle stress and metabolic reprogramming to potentiate antitumor immunity.Frontiers in immunology · 2026Review
- The role of ferroptosis in vascular endothelial cells and its role in the pathogenesis of cervical spondylosis of vertebral artery type: a comprehensive review.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas · 2026Review
- Borax Triggers Ferroptosis by Modulating the TfR1/GPX4/ACSL4 Pathway in Prostate Cancer Cells with Differential Androgen Sensitivity.Biological trace element research · 2025Article
- Non-coding RNAs-regulated SLC7A11 modulates ferroptosis: a new strategy for cancer therapy.Functional & integrative genomics · 2025Review
- Ferroptosis: biology and role in liver disease.Journal of gastroenterology · 2025Review
- Therapeutic targeting of cell death-immune crosstalk in cancer to rewire the tumor immune microenvironment.Molecular cancer · 2025Review
22 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ferroptosis is a type of regulated necrosis caused by unrestricted lipid peroxidation and subsequent plasma membrane rupture. However, the lipid remodeling mechanism that determines sensitivity to ferroptosis remains poorly understood. Here, we report a previously unrecognized role for the lipid flippase solute carrier family 47 member 1 (SLC47A1) as a regulator of lipid remodeling and survival during ferroptosis. Among 49 phospholipid scramblases, flippases, and floppases we analyzed, only SLC47A1 had mRNA that was selectively upregulated in multiple cancer cells exposed to ferroptotic inducers. Large-scale lipidomics and functional analyses revealed that the silencing of SLC47A1 increased RSL3- or erastin-induced ferroptosis by favoring ACSL4-SOAT1-mediated production of polyunsaturated fatty acid cholesterol esters. We identified peroxisome proliferator activated receptor alpha (PPARA) as a transcription factor that transactivates SLC47A1. The depletion of PPARA and SLC47A1 similarly sensitized cells to ferroptosis induction, whereas transfection-enforced re-expression of SLC47A1 restored resistance to ferroptosis in PPARA-deficient cells. Pharmacological or genetic blockade of the PPARA-SLC47A1 pathway increased the anticancer activity of a ferroptosis inducer in mice. These findings establish a direct molecular link between ferroptosis and lipid transporters, which may provide metabolic targets for overcoming drug resistance.
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