Iron, Lipids, and Cell Death: Advances in Ferroptosis Research

Iron, lipids, and cell death are increasingly recognized as central players in the pathogenesis of diverse diseases, particularly through their involvement in ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation. Unlike apoptosis, necroptosis, or pyroptosis, ferroptosis uniquely hinges on the dysregulation of iron metabolism and the depletion of antioxidant defenses, leading to catastrophic membrane damage via lipid peroxides. This distinct mechanism positions ferroptosis as a critical contributor to conditions ranging from neurodegeneration and ischemic organ injury to cancer and inflammatory disorders. The interplay between iron overload, polyunsaturated fatty acid metabolism, and redox imbalance further complicates disease progression, often exacerbating pathological outcomes. Given its mechanistic divergence from other cell death pathways, understanding ferroptosis has become imperative not only for unraveling disease etiologies but also for developing targeted therapies modulating iron homeostasis or lipid peroxidation.

Elucidating the intricate interplay between iron metabolism, lipid peroxidation, and ferroptosis holds immense potential for revolutionizing therapeutic strategies targeting cell death-driven pathologies. A critical gap persists in understanding the spatiotemporal dynamics of ferroptosis initiation and propagation, particularly how iron overload and dysregulated lipid remodeling converge to trigger membrane destabilization and oxidative catastrophe. Deciphering the molecular crosstalk between ferroptosis-specific drivers and cellular antioxidant defenses may unveil key regulatory nodes amenable to intervention. Leveraging these insights, developing robust diagnostic tools to detect ferroptosis-associated biomarkers, such as lipid peroxidation byproducts or iron flux signatures, could enable early identification of high-risk patients and real-time monitoring of therapeutic responses. Furthermore, novel therapeutic approaches encompassing iron chelators, radical-trapping antioxidants, or lipid peroxidation inhibitors may offer precise modulation of ferroptosis, mitigating its detrimental effects in degenerative diseases while harnessing its potential in cancer therapy. By bridging fundamental discoveries with translational applications, this research promises to advance ferroptosis therapeutics beyond conventional apoptosis-targeting paradigms, ushering in an era of selective and context-dependent cell death regulation with broad implications for disease treatment and tissue homeostasis.

Scope and information for authors
1. Mechanistic insights into ferroptosis, focusing on iron-dependent lipid peroxidation and its role in cell death.
2. Regulatory networks connecting ferroptosis to metabolic dysregulation, chronic diseases, and tissue injury.
3. The contribution of lipid-derived damage-associated molecular patterns (DAMPs) released during ferroptosis to inflammatory and immunological responses.
4. Biomarker development utilizing ferroptosis-related signatures for disease detection and therapeutic monitoring.
5. Novel therapeutics targeting ferroptosis pathways, including iron chelators, antioxidants, and lipid-modulating agents.
6. The influence of cellular metabolism and redox homeostasis on ferroptosis susceptibility and disease outcomes.
7. Epigenetic and post-translational control mechanisms modulating ferroptosis in pathological conditions.

Article types and fees

This Issue accepts the following article types, unless otherwise specified in the Issue description:

• Brief Communication
• Commentary
• Mini Review
• Original Research
• Review

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Issue accepts the following article types, unless otherwise specified in the Issue description:

• Brief Communication
• Commentary
• Mini Review
• Original Research
• Review

Keywords: Iron, Lipids, Cell Death, Apoptosis, Pyroptosis, Necroptosis, Ferroptosis, Autophagy