Autophagy promotes ferroptosis by degradation of ferritin
| Autor: | Wen Hou, Herbert J. Zeh, Daolin Tang, Xinxin Song, Rui Kang, Yangchun Xie, Michael T. Lotze, Xiaofang Sun |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Iron Nuclear Receptor Coactivators ATG5 Apoptosis Autophagy-Related Protein 7 Piperazines Autophagy-Related Protein 5 Lipid peroxidation Mice 03 medical and health sciences chemistry.chemical_compound Autophagy Animals Homeostasis Humans Letter to the Editor Molecular Biology Mice Knockout chemistry.chemical_classification Reactive oxygen species biology Cell Biology Fibroblasts Cell biology Pancreatic Neoplasms Ferritin 030104 developmental biology Biochemistry Nuclear receptor chemistry Ferritins Cancer cell biology.protein Lipid Peroxidation Reactive Oxygen Species Intracellular |
| Zdroj: | Autophagy. 12:1425-1428 |
| ISSN: | 1554-8635 1554-8627 |
| Popis: | Macroautophagy/autophagy is an evolutionarily conserved degradation pathway that maintains homeostasis. Ferroptosis, a novel form of regulated cell death, is characterized by a production of reactive oxygen species from accumulated iron and lipid peroxidation. However, the relationship between autophagy and ferroptosis at the genetic level remains unclear. Here, we demonstrated that autophagy contributes to ferroptosis by degradation of ferritin in fibroblasts and cancer cells. Knockout or knockdown of Atg5 (autophagy-related 5) and Atg7 limited erastin-induced ferroptosis with decreased intracellular ferrous iron levels, and lipid peroxidation. Remarkably, NCOA4 (nuclear receptor coactivator 4) was a selective cargo receptor for the selective autophagic turnover of ferritin (namely ferritinophagy) in ferroptosis. Consistently, genetic inhibition of NCOA4 inhibited ferritin degradation and suppressed ferroptosis. In contrast, overexpression of NCOA4 increased ferritin degradation and promoted ferroptosis. These findings provide novel insight into the interplay between autophagy and regulated cell death. |
| Databáze: | OpenAIRE |
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