Mechanisms of ferroptosis

By J. Cao, Scott J. Dixon. Cellular and Molecular Life Sciences, 2016

1,371 citations recorded by the source corpus.

Ferroptosis is a non-apoptotic form of cell death that can be triggered by small molecules or conditions that inhibit glutathione biosynthesis or the glutathione-dependent antioxidant enzyme glutathione peroxidase 4 (GPX4). This lethal process is defined by the iron-dependent accumulation of lipid reactive oxygen species and depletion of plasma membrane polyunsaturated fatty acids. Cancer cells with high level RAS-RAF-MEK pathway activity or p53 expression may be sensitized to this process. Conversely, a number of small molecule inhibitors of ferroptosis have been identified, including ferrostatin-1 and liproxstatin-1, which can block pathological cell death events in brain, kidney and other tissues. Recent work has identified a number of genes required for ferroptosis, including those involved in lipid and amino acid metabolism. Outstanding questions include the relationship between ferroptosis and other forms of cell death, and whether activation or inhibition of ferroptosis can be exploited to achieve desirable therapeutic ends.

Subfields: Cancer Research, Molecular Biology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/7465a80d59c67c6e7a7833b3b5efbaf145e595a2

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Citations in the corpus

GPx4, Lipid Peroxidation, and Cell Death: Discoveries, Rediscoveries, and Open Issues (2017, positive): “…mechanistic details about the involvement of iron handling, p53-dependent regulation of SLC7A11 (the substrate-speciﬁc subunit of system x c - ), and availability of cysteine via the trans-sulfuration pathway, which have been extensively illuminated in a recent comprehensive review article (16).”
Ferroptosis in cancer: from molecular mechanisms to therapeutic strategies (2024, background): “5 10 Mechanically, unlike classical RCD involving speci ﬁ c executioner proteins of cell death (such as gasdermin D for pyroptosis, caspase for apoptosis, and mixed lineage kinase domain-like protein (MLKL) for necrosis), the identity of the cell death executioner proteins in ferroptosis remains…”
Ferroptosis, a new form of cell death, and its relationships with tumourous diseases (2016, background): “Furthermore, the mechanisms underlying the induction of the key molecules, system XC and GPx4, in ferroptosis were partially revealed [2, 17].”
NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis (2019, background): “via buthionine sulfoximine) has also been shown to initiate ferroptosis [15].”
Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions (2022, background): “Ferroptosis is regulated by peroxidation, which requires sufficient accessible iron.(210) In ischemic brain regions, enhanced cellular excitotoxicity leads to the decrease in activity of GPX4 and reduction in GSH production,(211) which accumulates excessive ferric ion and subsequently induces ferrop”
The Development of the Concept of Ferroptosis (2018, neutral): “may overlap with ferroptosis in other cells [138].”
Ischemia/Reperfusion (2016, positive): “generation ferrostatins have been shown to decrease liver and kidney injury after I/R (110,117,250,455).”
13 reasons why the brain is susceptible to oxidative stress (2018, background): “However, as Cao & Dixon caution [90] despite redox commonalities glutamate ex-”
FINO2 Initiates Ferroptosis Through GPX4 Inactivation and Iron Oxidation (2018, neutral): “24, 25 The spirocyclic oxetanes were synthesized from cyclohexanones 5 - 7 in three steps.”