ROS-mediated autophagy increases intracellular iron levels and ferroptosis by ferritin and transferrin receptor regulation
By Eunhee Park, S. Chung. Cell Death and Disease, 2019
829 citations recorded by the source corpus.
Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation, leading to cell death. Recently, the induction of autophagy has been suggested during ferroptosis. However, this relationship between autophagy and ferroptosis is still controversial and the autophagy-inducing mediator remains unknown. In this study, we confirmed that autophagy is indeed induced by the ferroptosis inducer erastin. Furthermore, we show that autophagy leads to iron-dependent ferroptosis by degradation of ferritin and induction of transferrin receptor 1 (TfR1) expression, using wild-type and autophagy-deficient cells, BECN1+/− and LC3B−/−. Consistently, autophagy deficiency caused depletion of intracellular iron and reduced lipid peroxidation, resulting in cell survival during erastin-induced ferroptosis. We further identified that autophagy was triggered by erastin-induced reactive oxygen species (ROS) in ferroptosis. These data provide evidence that ROS-induced autophagy is a key regulator of ferritin degradation and TfR1 expression during ferroptosis. Our study thus contributes toward our understanding of the ferroptotic processes and also helps resolve some of the controversies associated with this phenomenon.
Subfields: Epidemiology, Hematology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/223783c0441759f4d9d2b010a5ebc871b1224cbc
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
- Mechanisms of neuronal cell death in ischemic stroke and their therapeutic implications (2021, background): “iron levels through ferritin degradation and induction of transferrin receptor 1 expression, therefore leading to ferroptosis.(468) Knockout or knockdown of autophagy‐related 5 (Atg5) and Atg7 limit erastin‐induced ferroptosis by decreasing intracellular ferrous iron levels and lipid peroxidation.”
- ROS-induced lipid peroxidation modulates cell death outcome: mechanisms behind apoptosis, autophagy, and ferroptosis (2023, background): “2021), and erastin promoted autophagy by promoting the AMPK pathway (Park and Chung 2019).”