Ferroptosis: Role of lipid peroxidation, iron and ferritinophagy.
By G. Latunde-Dada. Biochimica et Biophysica Acta - General Subjects, 2017
786 citations recorded by the source corpus.
Ferroptosis is a form of regulated cell death that is dependent on iron and reactive oxygen species (ROS) and is characterized by lipid peroxidation. It is morphologically and biochemically distinct and disparate from other processes of cell death. As ferroptosis is induced by inhibition of cysteine uptake or inactivation of the lipid repair enzyme glutathione peroxidase 4 (GPX4), the process is favored by chemical or mutational inhibition of the cystine/glutamate antiporter and culminates in the accumulation of reactive oxygen species (ROS) in the form of lipid hydroperoxides. Excessive lipid peroxidation leads to death by ferroptosis and the phenotype is accentuated respectively by the repletion and depletion of iron and glutathione in cells. Furthermore, oxidized phosphatidylethanolamines (PE) harbouring arachidonoyl (AA) and adrenoyl moieties (AdA) have been shown as proximate executioners of ferroptosis. Induction of ferroptosis due to cysteine depletion leads to the degradation of ferritin (i.e. ferritinophagy), which releases iron via the NCOA4-mediated autophagy pathway. Evidence of the manifestation of ferroptosis in vivo in iron overload mice mutants is emerging. Thus, a concerted synchronization of iron availability, ROS generation, glutamate excess and cysteine deficit leads to ferroptosis. A number of questions on the molecular mechanisms of some features of ferroptosis are highlighted as subjects for future investigations.
Subfields: Cancer Research, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/4a28a6128bcd4446765453a63f677d34fffedeeb
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Citations in the corpus
- Ferroptosis: mechanisms and links with diseases (2021, background): “Electrons may escape from oxidation-reduction reaction and be captured by O2 to form superoxide (O2•), peroxides (H2O2 and ROOH), and free radicals (HO• and RO•).(69) The oxidation by Fe and H2O2, which is called Fenton reaction, would provide hydroxyl radicals that subtract hydrogen (H) from lipid ”
- Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis (2019, background): “Imbalance in the rate of ROS generation leads to oxidative stress and consequent production of free radicals that can damage DNA, proteins, and lipids [10].”
- Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018 (2018, background): “Moreover, the toxicity of high extracellular glutamate may depend (at least in part) on the activation of ferroptosis through cysteine imbalance [534, 538, 552].”