ArticleCell death & disease2021
Acid sphingomyelinase-dependent autophagic degradation of GPX4 is critical for the execution of ferroptosis.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- Iron dysregulation in COVID-19 and reciprocal evolution of SARS-CoV-2: Natura nihil frustra facit.Journal of cellular biochemistry · 2022Pooled it
- GW4869 Depletes Macrophages and Increases Number of Extracellular Vesicles in Murine Peritoneal Cavity Fluid.Journal of extracellular biology · 2026Article
- Acid ceramidase modulates the lipid profile and exacerbates sensitivity to ferroptosis in WI-38 replicative senescent cells.Cell death & disease · 2026Article
- Selenoproteins: Minute yet vital players governing cellular fate.Genes & diseases · 2026Review
- Long-term inhibition of lysosomal glucocerebrosidase activity promotes GPX4 stability and inhibits ferroptosis in dopaminergic neurons.Cell death & disease · 2026Article
- Targeting ferroptosis in cancer: from mechanistic insights to therapeutic approaches.Molecular biomedicine · 2026Review
- Ly93 Inhibits Sphingomyelin Synthesis and Attenuates Inflammation and Injury in Dry Eye Conjunctival Organoids.Investigative ophthalmology & visual science · 2026Article
- Ferroptosis regulation in doxorubicin-induced cardiotoxicity: multi-mechanism interventions and translational strategies.Frontiers in pharmacology · 2026Review
- Convergent death programs in chronic obstructive pulmonary disease: how pyroptotic and ferroptotic crosstalk reshapes therapeutic paradigms.Frontiers in immunology · 2026Review
- Iron toxicity undermines microfracture-induced cartilage regeneration by predisposing a pre-ferroptotic niche.Frontiers in cell and developmental biology · 2026Article
- Ultrasound-Activated Nanoplatform Counteracts Triple-Negative Breast Cancer via Remodeling Intratumoral Microbiota-Metabolism and Inducing Ferroptosis.Biomaterials research · 2026Article
- Ferroptosis-Mediated Cell-Specific Damage: Molecular Cascades and Therapeutic Breakthroughs in Diabetic Retinopathy.Antioxidants (Basel, Switzerland) · 2025Review
- Polysaccharides from Huaier induce autophagy-dependent ferroptosis to inhibit breast cancer stem cells in triple-negative breast cancer.Cancer cell international · 2025Article
- Acid ceramidase modulates the lipid profile and exacerbates sensitivity to ferroptosis in senescent cells.Research square · 2025Article
- Pharmacological Inhibition of Ferroptosis Attenuates Experimental Abdominal Aortic Aneurysm Formation.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Targeting Nrf2 in acute myeloid leukemia: an updated review on its role in chemoresistance and emerging therapeutic strategies.Medical oncology (Northwood, London, England) · 2025Review
- BMAL1-depletion remodels ceramide metabolism to regulate ferroptosis and sorafenib chemosensitivity in acute myeloid leukemia.iScience · 2025Article
- Cell death crosstalk in respiratory diseases: unveiling the relationship between pyroptosis and ferroptosis in asthma and COPD.Molecular and cellular biochemistry · 2025Review
- Iron chelators loaded on myocardiocyte mitochondria-targeted nanozyme system for treating myocardial ischemia-reperfusion injury in mouse models.Journal of nanobiotechnology · 2025Article
- Alpha-synuclein aggregation induces prominent cellular lipid changes as revealed by Raman spectroscopy and machine learning analysis.Brain communications · 2025Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Ferroptosis is a type of regulated cell death characterized by ROS accumulation and devastating lipid peroxidation (LPO). The role of acid sphingomyelinase (ASM), a key enzyme in sphingolipid metabolism, in the induction of apoptosis has been studied; however, to date its role in ferroptosis is unclear. In this study, we report that ASM plays a hitherto unanticipated role in promoting ferroptosis. Mechanistically, Erastin (Era) treatment results in the activation of ASM and generation of ceramide, which are required for the Era-induced reactive oxygen species (ROS) generation and LPO. Inhibition of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) or removal of intracellular ROS, significantly reduced Era-induced ASM activation, suggesting that NADPH oxidase-derived ROS regulated ASM-initiated redox signaling in a positive feedback manner. Moreover, ASM-mediated activation of autophagy plays a critical role in ferroptosis inducers (FINs)-induced glutathione peroxidase 4 (GPX4) degradation and ferroptosis activation. Genetic or pharmacological inhibition of ASM diminishes Era-induced features of autophagy, GPX4 degradation, LPO, and subsequent ferroptosis. Importantly, genetic activation of ASM increases ferroptosis in cancer cells induced by various FINs. Collectively, these findings reveal that ASM plays a novel role in ferroptosis that could be exploited to improve pathological conditions that link to ferroptosis.
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