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Review
. 2017 Aug;1861(8):1893-1900.
doi: 10.1016/j.bbagen.2017.05.019. Epub 2017 May 24.

Ferroptosis: Role of lipid peroxidation, iron and ferritinophagy

Gladys O Latunde-Dada  1
Affiliations
Review

Ferroptosis: Role of lipid peroxidation, iron and ferritinophagy

Gladys O Latunde-Dada. Biochim Biophys Acta Gen Subj. 2017 Aug.

Abstract

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.

Keywords: Apoptosis; Autophagy; Ferritinophagy; Ferroptosis; Necrosis; Peroxidation.

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