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Short answer: Ferroptosis is a form of regulated cell death driven by iron-dependent accumulation of harmful lipid peroxides. It is distinct from apoptosis, necrosis and autophagy, and it is held in check by defence systems centred on GPX4 and FSP1. This page is general research information, not medical advice.
What is ferroptosis? Definition and scope
Yan and colleagues (2021) define ferroptosis as an iron-dependent cell death that differs from apoptosis, necrosis and autophagy. A 2022 review of FSP1 describes it as “a form of regulated cell death characterized by iron-dependent accumulation of harmful lipid peroxides.” Two practical consequences follow for the bench. Cells can be rescued by iron chelators (deferiprone, deferoxamine) and by small lipophilic antioxidants such as ferrostatin-1 and liproxstatin, and a death that is rescued this way is a candidate for ferroptosis rather than apoptosis. If you need the apoptosis side of that contrast, see what causes apoptosis.
Why is lipid peroxidation bad?
Membrane lipids can be oxidised to lipid hydroperoxides. Under normal conditions the enzyme GPX4 catalyses the reduction of specific lipid hydroperoxides, which keeps them from accumulating. When that protection fails, hydroperoxides build up in a way that is iron-dependent, and this accumulation is what defines ferroptosis. Reactive aldehydes such as 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) are described as major toxic products of lipid peroxidation.
How does FSP1 suppress ferroptosis?
FSP1 works in parallel to GPX4. It reduces ubiquinone (coenzyme Q10) to ubiquinol, consuming NAD(P)H, and ubiquinol limits the spread of lipid hydroperoxides. N-myristoylation of FSP1 is essential for its activity, and FSP1 can also reduce vitamin K to its hydroquinone form. Membrane repair through ESCRT-III components (CHMP5/6) is a separate route. A counter-screen in FSP1-overexpressing cells identified the inhibitor iFSP1, which sensitises cancer cells to ferroptosis; the review also notes that inhibiting GPX4 alone is not sufficient to induce ferroptosis in some cancer cell lines.
Defence axes and the compounds that hit them
This cross-walk of the reviews’ statements shows which compound targets which node, which is the logic behind choosing an inducer and a rescue agent in an experiment.
| Node | What it does (per the reviews) | Compound that targets it |
|---|---|---|
| System Xc- (cystine/glutamate antiporter) | Cystine uptake | Erastin inhibits cystine uptake |
| GPX4 | Reduces specific lipid hydroperoxides | RSL3 inhibits GPX4 by binding its active-site selenocysteine |
| FSP1 – CoQ10 – NAD(P)H axis | Reduces ubiquinone to ubiquinol, limiting lipid hydroperoxides | iFSP1 inhibits FSP1 |
| Radical trapping (rescue) | Traps lipid radicals | Ferrostatin-1 acts as a radical-trapping antioxidant |
Sorafenib is also named among ferroptosis inducers in the FSP1 review. Parallel systems involving DHODH and GCH1-BH4 have been reported as well.
Ferroptosis markers and assay readouts: a checklist
- Induce, then rescue. Show that the death caused by an inducer (for example erastin or RSL3) is prevented by ferrostatin-1 or liproxstatin, or by an iron chelator such as deferoxamine. Rescue is the core evidence that distinguishes ferroptosis from other death modes.
- Measure lipid peroxidation directly. BODIPY-C11 and LiperFluo are described as two major assays for lipid peroxidation in ferroptosis; LiperFluo is considered the more reliable probe because of its higher specificity.
- Treat MDA and 4-HNE as by-products. They are described as major toxic products of lipid peroxidation, not as formal ferroptosis-specific markers, so use them as supporting readouts only.
- Consider ACSL4. It is described as a biomarker and critical contributor to ferroptosis.
- Pair with a viability readout. Cell death measures such as a CCK-8 assay report loss of viability but not the mechanism; see also the cell proliferation assay guide. Apoptosis-specific assays such as the TUNEL assay address a different death route.
Record inducer, rescue agent, concentrations, cell line and probe in the methods so another lab can repeat the work; see reproducibility.
Common misunderstandings
- “Which foods trigger apoptosis?” This question mixes up two processes. Apoptosis and ferroptosis are different cell death mechanisms, and the reviews used for this page make no dietary claims for either. Nothing here is dietary advice.
- Ferroptosis is just oxidative damage. It is a regulated death programme with defined defence systems (GPX4, FSP1) and defined rescue agents.
- GPX4 inhibition always kills the cell. The FSP1 review notes it is insufficient in some cancer cell lines, because parallel systems compensate.
FAQ
What is ferroptosis?
An iron-dependent form of regulated cell death marked by accumulation of lipid peroxides, different from apoptosis, necrosis and autophagy.
Why is lipid peroxidation bad?
Lipid hydroperoxides in membranes accumulate when GPX4 and FSP1 protection fails, and in the presence of iron this leads to ferroptotic death. Its aldehyde products 4-HNE and MDA are described as toxic.
Which foods trigger apoptosis?
The cited reviews make no food claims. Apoptosis and ferroptosis are separate processes, and this page gives no dietary advice.
How does FSP1 suppress ferroptosis?
By reducing ubiquinone to ubiquinol using NAD(P)H, which limits lipid hydroperoxides, independently of GPX4.
Sources
- Yan H-F, et al. Ferroptosis: mechanisms and links with diseases. Signal Transduction and Targeted Therapy 2021;6:49 (PMC7858612). https://pmc.ncbi.nlm.nih.gov/articles/PMC7858612/. Read 2026-11-07.
- The anti-ferroptotic role of FSP1: current molecular mechanism and therapeutic approach. Molecular Biomedicine 2022 (PMC9708954). https://pmc.ncbi.nlm.nih.gov/articles/PMC9708954/; DOI https://link.springer.com/article/10.1186/s43556-022-00105-z. Read 2026-11-07.
