Lipid peroxidation and ferroptosis: The role of GSH and GPx4.
By F. Ursini, M. Maiorino. Free Radical Biology & Medicine, 2020
1,689 citations recorded by the source corpus.
Ferroptosis (FPT) is a form of cell death due to missed control of membrane lipid peroxidation (LPO). According to the axiomatic definition of non-accidental cell death, LPO takes place in a scenario of altered homeostasis. FPT, differently from apoptosis, occurs in the absence of any known specific genetically encoded death pathway or specific agonist, and thus must be rated as a regulated, although not "programmed", death pathway. It follows that LPO is under a homeostatic metabolic control and is only permitted when indispensable constraints are satisfied and the antiperoxidant machinery collapses. The activity of the selenoperoxidase Glutathione Peroxidase 4 (GPx4) is the cornerstone of the antiperoxidant defence. Converging evidence on both mechanism of LPO and GPx4 enzymology indicates that LPO is initiated by alkoxyl radicals produced by ferrous iron from the hydroperoxide derivatives of lipids (LOOH), traces of which are the unavoidable drawback of aerobic metabolism. FPT takes place when a threshold has been exceeded. This occurs when the major conditions are satisfied: i) oxygen metabolism leading to the continuous formation of traces of LOOH from phospholipid-containing polyunsaturated fatty acids; ii) missed enzymatic reduction of LOOH; iii) availability of ferrous iron from the labile iron pool. Although the effectors impacting on homeostasis and leading to FPT in physiological conditions are not known, from the available knowledge on LPO and GPx4 enzymology we propose that it is aerobic life itself that, while supporting bioenergetics, is also a critical requisite of FPT. Yet, when the homeostatic control of the steady state between LOOH formation and reduction is lost, LPO is activated and FPT is executed.
Subfields: Cancer Research, Pulmonary and Respiratory Medicine, Surgery
View Paper: https://www.semanticscholar.org/paper/79290390afecc927db72db0af762fdc13aec3b81
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Pulmonary and Respiratory Medicine
Citations in the corpus
- The cell biology of ferroptosis (2024, neutral): “For this reason, cells have evolved powerful enzyme-catalysed mechanisms to defend against oxidative membrane damage and the onset of ferroptosis 4,5 (Fig.”
- Ferroptosis in cancer: from molecular mechanisms to therapeutic strategies (2024, background): “119,120 Thus, the inactivation of GPX4 by both erastin and RSL3, either directly or indirectly, underscores the signi fi cance of GPX4 as a key repressor of ferroptosis.”