International consensus guidelines for the definition, detection, and interpretation of autophagy-dependent ferroptosis

Xin Chen*, Andrey S. Tsvetkov, Han Ming Shen, Ciro Isidoro, Nicholas T. Ktistakis, Andreas Linkermann, Werner J.H. Koopman, Hans Uwe Simon, Lorenzo Galluzzi, Shouqing Luo, Daqian Xu, Wei Gu, Olivier Peulen, Qian Cai, David C. Rubinsztein, Jen Tsan Chi, Donna D. Zhang, Changfeng Li, Shinya Toyokuni, Jinbao LiuJong Lyel Roh, Enyong Dai, Gabor Juhasz, Wei Liu, Jianhua Zhang, Minghua Yang, Jiao Liu, Ling Qiang Zhu, Weiping Zou, Mauro Piacentini, Wen Xing Ding, Zhenyu Yue, Yangchun Xie, Morten Petersen, David A. Gewirtz, Michael A. Mandell, Charleen T. Chu, Debasish Sinha, Eftekhar Eftekharpour, Boris Zhivotovsky, Sébastien Besteiro, Dmitry I. Gabrilovich, Do Hyung Kim, Valerian E. Kagan, Hülya Bayir, Guang Chao Chen, Scott Ayton, Jan D. Lünemann, Masaaki Komatsu, Stefan Krautwald, Ben Loos, Eric H. Baehrecke, Jiayi Wang, Jon D. Lane, Junichi Sadoshima, Wan Seok Yang, Minghui Gao, Christian Münz, Michael Thumm, Martin Kampmann, Di Yu, Marta M. Lipinski, Jace W. Jones, Xuejun Jiang, Herbert J. Zeh, Rui Kang, Daniel J. Klionsky*, Guido Kroemer, Daolin Tang*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Scopus)


Macroautophagy/autophagy is a complex degradation process with a dual role in cell death that is influenced by the cell types that are involved and the stressors they are exposed to. Ferroptosis is an iron-dependent oxidative form of cell death characterized by unrestricted lipid peroxidation in the context of heterogeneous and plastic mechanisms. Recent studies have shed light on the involvement of specific types of autophagy (e.g. ferritinophagy, lipophagy, and clockophagy) in initiating or executing ferroptotic cell death through the selective degradation of anti-injury proteins or organelles. Conversely, other forms of selective autophagy (e.g. reticulophagy and lysophagy) enhance the cellular defense against ferroptotic damage. Dysregulated autophagy-dependent ferroptosis has implications for a diverse range of pathological conditions. This review aims to present an updated definition of autophagy-dependent ferroptosis, discuss influential substrates and receptors, outline experimental methods, and propose guidelines for interpreting the results. Abbreviation: 3-MA:3-methyladenine; 4HNE: 4-hydroxynonenal; ACD: accidentalcell death; ADF: autophagy-dependentferroptosis; ARE: antioxidant response element; BH2:dihydrobiopterin; BH4: tetrahydrobiopterin; BMDMs: bonemarrow-derived macrophages; CMA: chaperone-mediated autophagy; CQ:chloroquine; DAMPs: danger/damage-associated molecular patterns; EMT,epithelial-mesenchymal transition; EPR: electronparamagnetic resonance; ER, endoplasmic reticulum; FRET: Försterresonance energy transfer; GFP: green fluorescent protein;GSH: glutathione;IF: immunofluorescence; IHC: immunohistochemistry; IOP, intraocularpressure; IRI: ischemia-reperfusion injury; LAA: linoleamide alkyne;MDA: malondialdehyde; PGSK: Phen Green™ SK;RCD: regulatedcell death; PUFAs: polyunsaturated fatty acids; RFP: red fluorescentprotein;ROS: reactive oxygen species; TBA: thiobarbituricacid; TBARS: thiobarbituric acid reactive substances; TEM:transmission electron microscopy.

Original languageEnglish
Pages (from-to)1213-1246
Issue number6
Early online date24 Mar 2024
Publication statusPublished - Jun 2024


  • Cell death
  • ferritinophagy
  • iron
  • lipid peroxidation
  • lipophagy
  • lysosome


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