Ferroptosis induces heterogeneous death profiles that are controlled by lysosome rupture
Year: 2026
Type: article
Abstract: Ferroptosis is a lipid peroxide-dependent form of cell death that occurs in degenerative conditions and may be leveraged for cancer therapy. Although numerous regulators are known to control its cell-autonomous execution, ferroptosis also has a collective property that involves propagation between cells, and this regulation has remained more obscure. Different modes of ferroptosis induction involving inhibition of the anti-ferroptotic enzyme GPX4 or depletion of glutathione can impact the collective death response differently, but the mechanisms underlying "single-cell" versus "propagative" ferroptosis are not well understood. Here, we discover significant lysosome rupture occurring during propagative ferroptosis and identify glutathione depletion as sufficient to convert GPX4 inhibition from an individual-cell response to a collective response. We find that induction of single-cell ferroptosis involves heterogeneous death profiles, with necrosis and apoptosis occurring in parallel within cell populations. These findings identify factors that control propagation and underscore lysosomes as critical to the execution of ferroptosis.
Source: Developmental Cell
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Funders: National Science Foundation, United States - Israel Binational Science Foundation, Memorial Sloan-Kettering Cancer Center, Starr Foundation, Commonwealth Foundation for Cancer Research Foundation, Ara Parseghian Medical Research Fund, Expect Miracles Foundation, United States-Israel Binational Science Foundation, National Institutes of Health, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke
Awards: G1533909524, G2377374449, G2462926169, Evolutionary and ecological dynamics of a contemporary climate-driven range expansion, G3031722201, G4091895087, Transient Metabolite Detection for Single-Cell Metabolomics and Diagnostics, G5075224004, G5605546136, CAREER: A Quantitative Nanosensor to Measure Redox Potential in Living Systems, G6386085371, G6412716416, G6671297155, G675646491, G7935922995, Ultrasmall particle-based solutions for inducing ferroptosis and improving anti-tumor immune responses in cancer, G9000010446, G9000031210, Ferroptosis and Cancer Cell Signaling
OpenAlex ID: W7129310075