Cited by 2,332Ferroptosis and cancer prognosisAutophagy in Disease and TherapyIron Metabolism and Disorders

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Autophagy promotes ferroptosis by degradation of ferritin

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Hou, Wen, Xie, Yangchun, Song, Xinxin, Sun, Xiaofang, Lotze, Michael T., Zeh, Herbert J., Kang, Rui, Tang, Daolin·2016·Autophagy

DOI 10.1080/15548627.2016.1187366PMC PMC4968231

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Abstract

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.

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Authors: Hou, W., Xie, Y., Song, X., Sun, X., Lotze, M. T., Zeh, H. J., Kang, R., & Tang, D.
Affiliations: University of Pittsburgh (US)
Third Affiliated Hospital of Guangzhou Medical University (CN)
Corresponding author: Tang, Daolin
ORCID: Xie, Yangchun
Song, Xinxin
Sun, Xiaofang
Lotze, Michael T.
Zeh, Herbert J.
Kang, Rui
Tang, Daolin
Venue: Autophagy
Publisher: Informa UK Limited
Published: 2016-06-24
Volume: 12
Issue: 8
Pages: 1425-1428
ISSN: 1554-8627 (ISSN-L)
1554-8635
DOI: 10.1080/15548627.2016.1187366
PMC: PMC4968231
OpenAlex: W2414659015
Cited by: 2,332
References: 28
Citations by year: 2026: 278 · 2025: 361 · 2024: 383 · 2023: 412 · 2022: 320 · 2021: 265 · 2020: 145 · 2019: 85 · 2018: 45 · 2017: 29 · 2016: 7
FWCI: 49.50
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Autophagy (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: University of Pittsburgh (P30 CA047904)
National Natural Science Foundation of China (201508020258, R01GM115366, 201400000004-4, RSG-16-014-01-CDD, P30CA047904, 201400000003, R01CA160417, 31171229, 201400000003-4, U1132005)
Natural Science Foundation of Guangdong Province (31171229, RSG-16-014-01-CDD, 201400000003-4, R01CA160417, U1132005, P30CA047904, 201400000004-4, R01GM115366, 201508020258)
National Institutes of Health (RSG-16-014-01-CDD)
Cancer Institute, University of Pittsburgh (RSG-16-014-01-CDD, R01GM115366, R01CA160417, P30CA047904)
National Cancer Institute (R01CA160417, R01CA181450, P30CA047904)
National Institute of General Medical Sciences (R01GM115366)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Keywords: ferroptosis, ferritinophagy, ferritin degradation, NCOA4, ATG5, ATG7, lipid peroxidation, iron homeostasis, selective autophagy, regulated cell death, erastin
MeSH terms: Autophagy-Related Protein 5, Autophagy-Related Protein 7, Animals, Autophagy, Ferritins, Fibroblasts, Homeostasis, Humans, Iron, Pancreatic Neoplasms, Piperazines, Lipid Peroxidation, Apoptosis, Reactive Oxygen Species, Mice, Knockout, Mice, Nuclear Receptor Coactivators

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Autophagy promotes ferroptosis by degradation of ferritin

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