ArticleAntioxidants (Basel, Switzerland)2026
Regulation of Ferroptosis Sensitivity in Hepatocellular Carcinoma Cells by Lysosomal Ion Channels TPC2 and TRPML1.
Article in Antioxidants (Basel, Switzerland), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Ferroptosis in metabolic dysfunction-associated steatotic liver disease.Frontiers in immunology · 2026Review
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Authors and funding
7 authors.
Funding
Abstract
Ferroptosis is an iron-dependent, lipid peroxidation-driven form of regulated cell death that has emerged as a therapeutic vulnerability in hepatocellular carcinoma (HCC), yet the contribution of lysosomes to this process remains incompletely understood. In this study, we investigated whether lysosomal ion channels regulate ferroptosis sensitivity in HCC cells, focusing on the two-pore channel 2 (TPC2) and the transient receptor potential mucolipin 1 (TRPML1). Using pharmacological modulation, genetic knockout models, flow cytometry-based cell death and lipid peroxidation assays, lipidomics, calcium measurements, and molecular analyses across multiple HCC cell lines, we examined how these channels influence ferroptotic signaling. We show that NAADP-dependent TPC2 activity is required for efficient ferroptosis induction, whereas TPC2 loss renders HCC cells resistant to ferroptosis triggered by system Xc
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