Ferroptosis Decoded: Tools and Insights to Unravel Iron-Driven Cell Death

Understanding Ferroptosis - A New Frontier in Cell Death and Disease

Ferroptosis is emerging as a pivotal biological process, an iron-dependent, regulated form of cell death driven by lipid peroxidation. Its implications span a wide range of diseases, including neurodegeneration, cancer, cardiovascular disorders, and kidney disorders. As such, it is no longer a scientific curiosity, but a fundamental pathway of both biological vulnerability and therapeutic potential.

Yet, studying ferroptosis presents real challenges. How can we accurately detect its early molecular events? How do we modulate it in a cell-specific manner? And how does it intersect with the broader redox and metabolic landscape of the cell?

Numerous metabolic pathways, including mitochondrial respiration, lipid handling, and amino acid metabolism, generate significant levels of reactive oxygen species (ROS), contributing to the onset of ferroptosis. For more on ROS generation and detection strategies, see our dedicated blog: Rethinking ROS Detection.

At Tebubio, we understand the complexities behind this iron-driven death pathway. That’s why we offer a comprehensive range of innovative tools to help you detect, quantify, and modulate ferroptosis across biological models.

Explore this article

Ferroptosis: At the Crossroads of Iron, Lipids, and ROS

Ferroptosis is defined by the iron-dependent accumulation of lipid peroxides, culminating in plasma membrane rupture (Figure 1). Triggered by an excess of intracellular ferrous iron (Fe²⁺) and the peroxidation of polyunsaturated fatty acids (PUFAs), ferroptosis is fundamentally distinct from apoptosis or necroptosis.

Figure 1: Schematic overview of the progression of ferroptosis, marked by lipid peroxidation and culminating in plasma membrane rupture.

The key antioxidant enzyme GPX4 (glutathione peroxidase 4) serves as a critical gatekeeper, reducing toxic lipid hydroperoxides using glutathione (GSH) (Figure 2). Blocking this pathway, e.g., via Erastin, which inhibits cystine uptake and depletes GSH, renders cells highly susceptible to ferroptotic death.

Furthermore, mitochondria and lysosomes add additional layers of regulation. Mitochondrial metabolism fuels ROS production, iron utilisation, and lipid processing. Lysosomal iron release and lipid catabolism further amplify peroxidative stress.

Figure 2: Inducers (red), and inhibitors (blue) of ferroptosis. GPX4 protects cells from lipid peroxidation; its inhibition by the depletion of GSH, or more directly through its binding with molecules such as RSL3, triggers the accumulation of lipid oxygen reactive species (ROS), and triggers cell death.

What makes ferroptosis so intriguing? Virtually any iron- and PUFA-containing cell under oxidative stress could be vulnerable, posing both a threat and a therapeutic opportunity.

A Rising Star in Pathophysiology

Recent publications [(PubMed IDs: 40464746; 40335696; 40551269)] highlight ferroptosis as a potential driver of disease progression, but also as a target for intervention.

Ferroptosis plays a role in various diseases, including neurodegeneration, cardiovascular diseases, kidney disorders, and various types of cancer.

Figure 3: A growing number of diseases are being linked to ferroptosis, including cancer, neurodegenerative, cardiovascular, and renal conditions. In cancer, ferroptosis inducers may selectively kill tumour cells with disrupted iron homeostasis. In neurodegenerative disorders, excessive lipid peroxidation and iron mismanagement are central contributors. In cardiovascular disease, ferroptotic damage has been linked to myocardial infarction and atherosclerosis.

However, while our mechanistic understanding has advanced, key questions remain:

• Which cellular subpopulations are most ferroptosis-prone?
• How do tumour microenvironments or inflammatory cues modulate ferroptosis sensitivity?
• What are the most robust biomarkers of ferroptosis in vivo?

This is where Tebubio’s tools come in to transform your hypothesis into data.

Tebubio's Ferroptosis Toolbox: Detect, Quantify, Understand

Whether you're investigating early lipid peroxidation events or quantifying intracellular Fe²⁺ levels, we offer high-performance reagents optimised for live-cell imaging, flow cytometry, microscopy, and plate-reader assays.

Lipid Peroxidation and Iron Detection

Figure 4: Fluorescence images of lipid peroxidation in A549 cells stimulated by erastin. A stronger fluorescent signal of Liperfluo (L248) was observed in the ferroptosis-induced sample (left panel). Fluorescence images of lipid peroxidation in HeLa cells (in the right panel).

Figure 5: The fluorescence intensity of FerroOrange (F374) was increased in HeLa cells treated with Ammonium iron (II) sulfate (B) compared with the findings in untreated cells (A); conversely, its fluorescence intensity was decreased in cells treated with Bpy (C).

Quantitative Ferroptosis Analysis

These tools allow for multi-parameter ferroptosis profiling, a must for studies dissecting both early redox stress and terminal cell death.

Key Metabolic Assays - Uncovering the Ferroptotic Axis

Explore the enzymatic machinery involved in ferroptosis, from the antioxidant response to PUFA metabolism.

These assays are ideal for uncovering mechanistic insights, testing ferroptosis inhibitors or evaluating antioxidant therapies.

Control the Pathway: Ferroptosis Modulators at Your Fingertip

Tebubio offers a wide panel of well-characterised ferroptosis modulators, helping you induce, inhibit or activate the ferroptotic cascade with precision.

Inducers

• Erastin – GSH depletion
• RSL3 – Direct GPX4 inhibitor
• FIN56, ML210, Altretamine – Various mechanisms

Inhibitors

• Ferrostatin-1, Liproxstatin-1, icFSP1, iFSP1, 7-Dehydrocholesterol, SRS16-86 – Inhibit lipid peroxidation and protect against ferroptosis
• Deferasirox, Dexrazoxane, Nocardamine, UAMC-4821 – Chelate iron and reduce ferroptotic stress

   

• E3330 – Redox modulator via APE1/Ref-1 inhibition

These inhibitors act at key regulatory checkpoints, blocking iron overload, scavenging lipid radicals, or boosting antioxidant defences, to suppress ferroptosis across diverse models.

Looking for a particular inhibitor or a specific combination for your screening assays? Our team can assist with tailored synthesis and sourcing, and compound pairing strategies to match your experimental needs.

Activators

• 4-Octyl Itaconate – Nrf2 pathway activation
• Arvanil – Endocannabinoid system modulator

Need something specific? We can support custom synthesis and sourcing or compound pairing for high-throughput screening projects. 

Need to Go Further? We’ve Got You Covered

Whether you're exploring ferroptosis for the first time or designing advanced functional studies, Tebubio provides more than reagents, we deliver solutions. Our offer includes ready-to-use probes, assays, and modulators, but also Contract Research Services tailored to your experimental models and research questions.

From assay optimisation and screening to protocol development or sourcing of niche compounds, our team of Project Managers is ready to support you throughout your project. Let’s co-design your next breakthrough.

Toward a New Standard in Ferroptosis Research

Ferroptosis is no longer a conceptual frontier; it’s a critical axis in both basic and translational research. As the field matures, there’s a growing need for reliable, easy-to-use, and validated tools that keep pace with scientific innovation.

At Tebubio, we’re committed to enabling your discoveries with high-quality reagents and personalised support. Join the next wave of cell death research and make your ferroptosis studies more reproducible, insightful, and impactful.

• References

  Source 1: Zhao, Yiheng et al. “Ferroptosis in cardiovascular disease: regulatory mechanisms and therapeutic implications.” European heart journal, ehaf374. 4 Jun. 2025, doi:10.1093/eurheartj/ehaf374.
  Source 2: Cañeque, Tatiana et al. “Activation of lysosomal iron triggers ferroptosis in cancer.” Nature vol. 642,8067 (2025): 492-500. doi:10.1038/s41586-025-08974-4.
  Source 3: Wei, Hongyun et al. “Predicting prognosis and immunotherapy response of ferroptosis-related genes in colorectal cancer.” European journal of medical research vol. 30,1 508. 23 Jun. 2025, doi:10.1186/s40001-025-02779-x.
  Figure 1: Dixon SJ, Olzmann JA.The cell biology of ferroptosis. Nat Rev Mol Cell Biol. 2024 Jun;25(6):424-442. doi: 10.1038/s41580-024-00703-5. Epub 2024 Feb 16. PMID: 38366038; PMCID: PMC12187608.
  Figure 2: Agmon, E., Solon, J., Bassereau, P. et al. Modeling the effects of lipid peroxidation during ferroptosis on membrane properties. Sci Rep 8, 5155 (2018). https://doi.org/10.1038/s41598-018-23408-0
  Figure 3: Dr. Mariia Kuzina. Lipids promote ferroptosis in cancer cells. Lipotype.com.
  Figures 4 & 5: Courtesy of Dojindo, your trusted supplier for ferroptosis detection probes.

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