NCOA4-mediated ferritinophagy promotes ferroptosis induced by erastin, but not by RSL3 in HeLa cells
نویسندگان
چکیده
Ferroptosis is a regulated cell death characterized by lethal accumulation of lipid peroxides due to an increase intracellular iron and decrease antioxidant capacity. The reduction activity obtained using chemical agents, such as erastin RSL3, the first one inhibiting transmembrane cystine-glutamate antiporter causing cysteine glutathione depletion second inactivating directly peroxidase 4 (GPX4) respectively. role its related proteins in supporting formation peroxides, not completely understood hence try shed light on it we generated HeLa clones with altered ferritinophagy, ferritin degradation process, knocking-out or overexpressing Nuclear Receptor Coactivator (NCOA4), autophagic cargo-receptor. NCOA4 deficiency abolished ferritinophagy increasing level making cells more resistant erastin, but unexpectedly sensitive RSL3. Interestingly, found that promoted expressing NCOA4, free iron, peroxidation sensitivity ferroptosis. In contrast, RSL3 did modulate while overexpression delayed RSL3-induced suggesting mechanism action independent process. Therefore, ferritin-iron release execution ferroptosis seems depend inducing compound, target downstream pathway activation. • Erastin induces NCOA4-mediated for RSL3-mediated ferroptotic does involve expression and/or active delay Abbrevations. BH tetrahydrobiopterin CoQ 10 coenzyme Q Cys Cys-Cys cystine DFO desferoxamine ER FAC ferric ammonium citrate Fer-1 ferrostatin-1 FSP1 suppressor protein 1 FTH heavy chain FTL FPN ferroportin GAPDH glyceraldehyde 3-phosphate dehydrogenase GCH1 GTP cyclohydrolase-1 Glu glutamine GPX4 GSH GSSG oxidized HO-1 heme oxygenase LC3 (MAP1LC3) microtubule-associated 3 LIP labile pool LOX5 lipoxygenase 5 nuclear receptor coactivator NRF2 factor erythroid 2 (NFE2)-related NQO1 NAD( P )H quinone ROS reactive oxygen species RAS-selective TfR1 transferrin TxnR thioredoxin reductase
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ژورنال
عنوان ژورنال: Biochimica et biophysica acta. Molecular cell research
سال: 2021
ISSN: ['0167-4889', '1879-2596']
DOI: https://doi.org/10.1016/j.bbamcr.2020.118913