ROS-mediated autophagy increases intracellular iron levels and ferroptosis by ferritin and transferrin receptor regulation

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 c...

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Vydáno v:	Cell death & disease Ročník 10; číslo 11; s. 822 - 10
Hlavní autoři:	Park, Eunhee, Chung, Su Wol
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 28.10.2019 Springer Nature B.V
Témata:	13/109 13/2 13/31 631/80/82/23 631/80/82/39 64/60 82/1 82/29 82/80 Antibodies Antigens, CD - genetics Apoptosis Apoptosis - genetics Autophagy Autophagy - genetics Beclin-1 - genetics Biochemistry Biomedical and Life Sciences Cell Biology Cell Culture Cell death Cell survival Cytoplasm - genetics Cytoplasm - metabolism Ferritin Ferroptosis Ferroptosis - drug effects Ferroptosis - genetics Humans Immunology Intracellular Iron Iron - metabolism Life Sciences Lipid peroxidation Lipid Peroxidation - genetics Microtubule-Associated Proteins - genetics Phagocytosis Piperazines - toxicity Reactive oxygen species Reactive Oxygen Species - metabolism Receptors, Transferrin - genetics Transferrins
ISSN:	2041-4889, 2041-4889
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-4889 2041-4889
DOI:	10.1038/s41419-019-2064-5