Metabolism and iron signaling in ferroptotic cell death
Open accessAbstract
Programmed cell death (PCD) plays critical roles in development and tissue homeostasis of multicellular organisms, and malfunction of programmed cell death contributes to the pathogenesis of a variety of human diseases, including cancer [1]. While apoptosis had been the main focus of the PCD study for decades, recent advances demonstrate that there exist multiple other forms of cell death that are also genetically “programmed”, such as receptor-interacting protein kinase 3 (RIPK3)-dependent necroptosis and iron-dependent ferroptosis [1].
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Glutamine and transferrin induce ferroptosis under serum-deprivation conditions through glutaminolysis.
“Glutamine and transferrin were found to induce ferroptosis under serum-deprivation conditions, via the glutaminolysis pathway [38, 39].”
From Ferroptosis: Death by Lipid Peroxidation (2016) · cites this paper as [39]
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“Glutamine and transferrin were found to induce ferroptosis under serum-deprivation conditions, via the glutaminolysis pathway [38, 39].”
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“Exogenous iron could boost the components of ferroptosis and morphological aspects of cell death, as previously described, and it is believed that disturbed iron metabolism is primarily responsible for ferroptosis [34, 35].”
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“Thus, an increase in HSPB1 expression can prevent ferroptosis (18, 19).”
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“These markers are critical indicators of the advancement and progression of ferroptotic cell death (Gao et al., 2015).”
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“However, when excess free Fe2+ is present in the cell, ferritin is recruited and solubilized by specific cargo receptor recognition, and the released excess Fe2+ in turn increases the formation of hydroxyl radicals through the Fenton reaction, inducing reactive oxygen species (ROS) production and increased susceptibil…”
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Khorsandi, K., Esfahani, H., Keyvani‐Ghamsari, S., & lakhshehei, P. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01296-w · Cited by 44 · see citing works
“These drugs induce ferroptosis, which has an anticancer effect [21, 22].”
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“Overexpression of heat shock protein B1 and suppressing the iron metabolism master regulator iron-responsive element-binding protein 2 resulted in a decrease in intracellular iron, thereby inhibiting ferroptosis [19,20].”
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“HSPB1 is a chaperone of the small heat shock protein (sHsp) group and it can reduce the contents of ferric iron by inhibiting the expression of TFR1, further alleviating ferroptosis [46].”
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“HSPB1 can reduce the concentration of Fe3+ by inhibiting the express of TFR1 and further ease the intensity of ferroptosis (38).”
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“As mentioned earlier the presence of exogenous iron can enhance cellular ferroptosis and alter the morphology of cells, in which iron metabolism disorders are believed to be the primary cause of ferroptosis (Dixon & Stockwell, 2014; Gao et al., 2015).”
BackgroundA ferroptosis-related lncRNA signature predicts prognosis in ovarian cancer patients
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“Regulated cell death (RCD) plays an invaluable role in the occurrence and development of tumors (6).”
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“HSPB1 is a molecular chaperone of several small heat shock proteins, which can reduce the concentration of Fe3+ by inhibiting the expression of TFR1, thereby alleviating the intensity of ferroptosis [41].”
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Si, C., Zhou, X., Deng, J., Ye, S., Kong, L., Zhang, B., & Wang, W. (2022) · Cell Biology International · doi:10.1002/cbin.11804 · Cited by 18 · see citing works
“Numerous biological processes are involved in ferroptosis, among which, glutamate and glutamine are key regulators of ferroptosis (Gao et al., 2015).”
BackgroundFerroptosis, Acyl Starvation, and Breast Cancer
Bobiński, R., Dutka, M., Pizon, M., Waksmańska, W., & Pielesz, A. (2022) · Molecular Pharmacology · doi:10.1124/molpharm.122.000607 · Cited by 19 · see citing works
“By regulating the expression of transferrin receptor (TFRC) and ferritin heavy chain 1, etc., IRP1 and IRP2 stabilize the cell ’ s labile iron pools composed of Fe 2 1 .”
InfluentialThe Regulation Role of Ferroptosis Mechanism of Anti-Cancer Drugs and Noncoding RNAs
Ensoy, M., Bumin, Z. S., Jama, H. A., & Cansaran‐Duman, D. (2022) · Current Medicinal Chemistry · doi:10.2174/0929867329666220629154418 · Cited by 17 · see citing works
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“[17] Additionally, α-tocopherol, an endogenous inhibitor of lipid peroxidation, has been found to impede ferroptosis by intervening in this pathway.[18] Furthermore, numerous studies have elucidated the connection between ferroptosis and ROS.”
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“It has been shown that glutamine metabolism, known as glutaminolysis (conversion of glutamine to alpha-ketoglutarate), is required for cysteine deprivation-induced ferroptosis [31,32].”
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“Studies have shown that fatal lipid peroxidation [20] is a cause of ferroptotic cell death (Gao et al., 2015).”
BackgroundFerroptosis in cardiovascular diseases: molecular mechanisms and a novel therapeutic target
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“Yang et al. [233] and Koleini et al. [234] identified a key role for ferroptosis in DOX-induced HF. DOX induces intracellular accumulation of oxidized phospholipids, which upregulates HO-1 expression via Nrf2, leading to cardiac heme degradation and release of free iron.”
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Identification of Ferroptosis Biomarker in AHH-1 Lymphocytes Associated with Low Dose Radiation
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Autophagy-dependent ferroptosis may play a critical role in early stages of diabetic retinopathy
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“Regulated cell death has a critical role in normal homeostasis and development [10].”
BackgroundPhytoconstituents-mediated Targeting of Ferroptosis for the Treatment of Cardiovascular Disease
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“Moreover, heat shock protein B1 (HSPB1) reduces intracellular iron levels and increases cell resistance to ferroptosis in this manner [26].”
Yeni Bir Hücre Ölüm Şekli Olarak Ferroptozis
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The Key of the Terminal Stage of Vitiligo: The Death Form of Melanocytes
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“Studies found that the metabolism of amino acids such as glutamine is a key step in this process, and ultimately leads to the occurrence of ferroptosis through ROS [37].”
Regulatory mechanism of ferroptosis, a new mode of cell death
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“Thus, overexpressed HSPB1 can inhibit ferroptosis [26].”
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Research Progress on Ferroptosis as a Therapeutic Strategy in Renal Cell Carcinoma
Liu, M., Bai, M., Cui, N., Ding, Y., & Zhang, P. (2022) · annals of urologic oncology · doi:10.32948/auo.2022.12.09
“These functional proteins participate in iron metabolism, including ferritin light chains (FTL), ferritin heavy chain (FTH1), ferritin transfer protein (FPN), transferrin receptor 1 (TFR1) during iron intake, and iron regulating proteins 1, 2 (IRP1/2 ) [11-13].”
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“Consequently, the inhibition of SLC7 A11 can induce cell death through ferroptosis[46–49].”
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- Authors
- Gao, M., Monian, P., & Jiang, X.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2015-09-15
- Volume
- 6
- Issue
- 34
- Pages
- 35145-35146
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC4742090
- OpenAlex
- W2187950219
- Cited by
- 71
- References
- 7
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 9 · 2023: 5 · 2022: 18 · 2021: 15 · 2020: 5 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 1
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Oncotarget (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA166413, P30CA008748)
- National Institute of General Medical Sciences (R01GM113013)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Keywords
- ferroptosis, iron signaling, programmed cell death, iron metabolism, apoptosis, cancer
- MeSH terms
- Animals, Glutamine, Humans, Iron, Transferrin, Signal Transduction, Apoptosis, Mice, Knockout, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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