ArticleNature communications2025
Senescence-associated lysosomal dysfunction impairs cystine deprivation-induced lipid peroxidation and ferroptosis.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Cellular senescence and regulated cell death in cancer: mechanisms, cross-regulatory networks and therapeutic implications.Journal of hematology & oncology · 2026Review
- Ferroptosis and Ferro-Aging in Obesity: Bibliometric Mapping, Shared Mechanisms, and Translational Perspectives.Metabolites · 2026Review
- TLDc proteins: Stress-responsive nexus regulators of redox signaling, V-ATPase dynamics, and organellar crosstalk in neurodegeneration.Redox biology · 2026Review
- Ferroptosis-Senescence Crosstalk in Sepsis-Associated Acute Lung Injury: Mechanisms and Therapeutic Opportunities.Biomedicines · 2026Review
- Proteome-Level Autophagy-Lysosome Remodelling Marks Ageing in Human Dermal Fibroblasts and Nominates Hydroxytyrosol as a Candidate Nutraceutical.International journal of molecular sciences · 2026Article
- Compartmental pH regulation in cancer and antitumor immunity: therapeutic opportunities and challenges.Apoptosis : an international journal on programmed cell death · 2026Review
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- Lysosomes in Ferroptosis: Regulatory Mechanisms and Molecular Targets.Molecules (Basel, Switzerland) · 2026Review
- Review
- Cell size modulates ferroptosis susceptibility.eLife · 2026Article
- Fatty acid channelling into triglycerides and oxylipins drives ferroptosis resistance during oncogenic BRAF-induced senescence.Cell death and differentiation · 2026Article
- Lysosomal Profiling with LysoTracker for Quantitative Assessment of Cellular Senescence in Human Fibroblasts.bioRxiv : the preprint server for biology · 2026Article
- Cell size modulates ferroptosis susceptibility.bioRxiv : the preprint server for biology · 2026Article
- Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming.npj aging · 2026Review
- In Situ Synthesis of Covalent Organic Frameworks Inside Cells for Triggering Ferroptosis and Immunotherapy.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Exercise mitigates Alzheimer's disease by targeting ferroptosis driven by cellular senescence.Frontiers in cell and developmental biology · 2025Review
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Authors and funding
15 authors.
Funding
Abstract
Senescent cells, characterized by irreversible cell cycle arrest and inflammatory factor secretion, promote various age-related pathologies. Senescent cells exhibit resistance to ferroptosis, a form of iron-dependent cell death; however, the underlying mechanisms remain unclear. Here, we discovered that lysosomal acidity was crucial for lipid peroxidation and ferroptosis induction by cystine deprivation. In senescent cells, lysosomal alkalinization causes the aberrant retention of ferrous iron in lysosomes, resulting in resistance to ferroptosis. Treatment with the V-ATPase activator EN6 restored lysosomal acidity and ferroptosis sensitivity in senescent cells. A similar ferroptosis resistance mechanism involving lysosomal alkalinization was observed in pancreatic cancer cell lines. EN6 treatment prevented pancreatic cancer development in xenograft and Kras mutant mouse models. Our findings reveal a link between lysosomal dysfunction and the regulation of ferroptosis, suggesting a therapeutic strategy for the treatment of age-related diseases.
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